Mutagenesis Advance Access originally published online on April 13, 2006
Mutagenesis 2006 21(3):205-211; doi:10.1093/mutage/gel016
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Possible involvement of XPA in repair of oxidative DNA damage deduced from analysis of damage, repair and genotype in a human population study
inská1,*
upinková11 Department of Experimental and Applied Medicine, Institute of Preventive and Clinical Medicine, Research Base of Slovak Medical University Limbová 14, 83303 Bratislava, Slovakia 2 School of Life Sciences, Robert Gordon University Aberdeen, UK 3 Department of Nutrition, University of Oslo Oslo, Norway
Participants in a study of occupational exposure to mineral fibres in Slovakia were analysed for the polymorphism 23A
G in the DNA repair gene XPA. Of the 388 subjects, 239 were exposed to asbestos, stonewool or glass fibre; the rest were unexposed controls. Levels of DNA base alterations (oxidation and alkylation) in lymphocytes were measured using the comet assay with lesion-specific endonucleases. 8-oxoguanine DNA glycosylase (OGG1) DNA repair activity was measured, as incision activity of a lymphocyte extract on DNA containing the OGG1 substrate 8-oxoguanine. Presence of the A allele was associated with higher levels of DNA damage (sites sensitive to formamidopyrimidine DNA glycosylase, endonuclease III or 3-methyladenine DNA glycosylase II) as well as with higher activity of OGG1 repair enzyme. DNA base damage increased with age, showing highly significant correlations when the whole population or subgroups of the population were analysed. OGG1 repair activity also increased with age, but when analysed according to XPA genotype, the increase was observed only in those individuals with an A allele. Although XPA is known as a protein involved in nucleotide excision repair of UV-induced damage and bulky DNA adducts, it may also have a role in the repair of oxidized bases.
 |
Introduction |
|---|
 Top Introduction Materials and methodsResultsDiscussionReferences |
|---|
Different kinds of DNA damage in mammalian cells are dealt with by different repair pathways. Bulky adducts and helix distortions in DNA are substrates for nucleotide excision repair (NER), whereas smaller lesions such as oxidized or alkylated bases are recognized by specific glycosylases at the initial stage of base excision repair (BER). The NER pathway has been particularly well characterized and is known to involve about 30 polypeptides (1
) of which several were identified by investigation of the genetic defects in the rare human disease xeroderma pigmentosum (XP). One of the components in this pathway is XPA, a 32 kDa zinc-finger DNA-binding protein, which interacts with several of the other NER proteins (2). The mechanism of damage recognition is not entirely clear (3). Wakasugi and Sancar (4) assessed the binding to damaged DNA of different combinations of these repair proteins. They describe a model in which initial recognition of damage is carried out by replication protein A (RPA) or a complex of RPA and XPA; with the subsequent addition of XPC and transcription factor IIH (TFIIH), a stable pre-incision complex, of high specificity, is formed. XPG and XPF-ERCC1 are then added to the complex and perform the dual incisions on either side of the bound lesion. However, the widely accepted view now is that damage recognition is accomplished by XPC, together with the protein hHR23B; after binding of this complex, XPA is involved in verification of the damaged substrate and positioning of the endonucleases (XPG and XPF-ERCC1) for excision of the damage-containing oligonucleotide (5).
Mutations in XP genes, causing more or less complete lack of NER, are very rare and account for the extreme sun-sensitivity and incidence of skin cancer in XP patients (6). There are, however, common polymorphisms in XP that, if they change the amino acid sequence of the protein or level of expression of the gene, may have more subtle effects on the efficiency of NER and, hence, influence individual risk of cancer. Butkiewicz et al. (7) described two polymorphisms in XPA: one occurring at a frequency of just over 1% and causing a substitution of A for G at position 709; and another much more common variant, in the 5' non-coding region of the gene (position 23, 4 nt before the ATG start codon), where A and G are found at roughly equal frequencies.
Park et al. (8) carried out XPA genotyping on 265 lung cancer patients and 185 healthy age-matched and sex-matched controls. They found that the XPA 23GG genotype was associated with a significantly decreased risk of lung cancer when compared with AA and AG genotypes combined. An apparent protection against lung cancer was also reported by Wu et al. (9). In their comparison of 695 lung cancer patients and 695 matched controls, the presence of one or two copies of the G allele was associated with a lower risk of lung cancer, significant for Caucasians and Mexican-Americans though not for African-Americans. A Caucasian subset of this population was previously assessed for NER capacity using a host cell reactivation assay based on the ability of lymphocytes to repair benzo[a]pyrene diolepoxide adducts in transfected plasmid DNA (10). For 284 of the Caucasian cases and 376 controls, it was possible to relate repair capacity to genotype. In the control group, but not the cases, presence of the G allele was associated with significantly higher repair rates (9). Butkiewicz et al. (11) also observed an increase in lung cancer risk in subjects who had the AA genotype—significant in heavy smokers and occupationally exposed subjects, which implies an interaction between environmental insult and genotype.
The Fibretox project (funded by the European Commission) examined the effects of occupational exposure to mineral fibres on various biomarkers, including DNA damage and repair. In view of the link between asbestos exposure and lung cancer, we decided to study the relationship between phenotypic biomarkers and XPA genotype. A total of 239 workers with occupational exposure to asbestos, stonewool or glass fibre were investigated along with 149 unexposed subjects. The comet assay—a simple, sensitive method for measuring DNA breaks—was used in conjunction with lesion-specific glycosylases/endonucleases to measure, in addition to breaks, oxidized pyrimidines, oxidized purines and alkylation damage in the DNA of lymphocytes (12,13 and our unpublished results). We also measured the activity of the repair enzyme 8-oxoguanine DNA glycosylase (OGG1) using an in vitro assay with DNA containing 8-oxoGua as a substrate.
|
Materials and methods |
|---|
|
TopIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Subject selection and sampling
Workers at industrial plants in three towns in Slovakia (Nitra, Nová Ba
a and Trnava) with at least 5 years exposure to asbestos, stonewool or glass fibres were recruited for this study (12,13 and our unpublished results). We investigated 239 workers in three factories with occupational exposure to asbestos (n = 61), stonewool (n = 97) or glass fibre (n = 81), together with 149 controls matched for age, sex, alcohol and cigarette use. Controls came from factory administrative staff with no history of exposure to fibres: 43 in the stonewool factory and 36 in the glass fibre factory. In the case of the asbestos factory, only 21 administrative staff were available, and therefore 49 matched local residents not connected with the factory were recruited to make up the required number. (These two subgroups did not differ in the measured parameters.) The sampling was carried out in September 2000 (asbestos-exposed and stonewool-exposed subjects and controls) and in September 2001 (exposed subjects and controls from the glass fibre factory). The participants were interviewed by trained personnel and answered detailed questionnaires relating to duration of fibre exposure, smoking, alcohol consumption, nutritional habits and lifestyle. Smoking status was confirmed by cotinine measurement in urine. All workers underwent clinical examination, including a functional spirometry test, radiological and immunological examinations; a manuscript describing these clinical results is in preparation. From each subject 30 ml of blood was obtained by venepuncture. A urine sample was used for measurement of cotinine to determine smoking status. The blood samples were used for extraction of DNA (for genotype analysis), and separation of plasma (for various biochemical measurements), as well as to obtain the lymphocytes employed in the studies reported here.
All study participants signed an informed consent form. This study was approved by the Ethical Committee of the Research base of the Slovak Medical University (the Institute of Preventive and Clinical Medicine) in Bratislava.
Isolation of lymphocytes
After centrifugation of blood for collection of plasma, the buffy coat was recovered and mixed with RPMI 1640 medium with 10% fetal calf serum (FCS) before layering over an equal volume of Lymphoprep (Nycomed, Oslo, Norway) and centrifuging at 700x g for 20 min at 20°C. The layer above the Lymphoprep, containing lymphocytes, was removed, diluted with medium and centrifuged at 700x g for 15 min at 20°C. Lymphocytes were used immediately for estimation of DNA damage, while surplus cells were suspended in 90% FCS and 10% DMSO, divided into aliquots and frozen slowly to –80°C. For the DNA repair assay, lymphocytes (5 x 106 in 50 µl aliquots) were snap-frozen in liquid nitrogen in 45 mM HEPES, 0.4 M KCl, 1 mM EDTA, 0.1 mM dithiothreitol and 10% glycerol, pH 7.8.
Measurement of DNA damage
The comet assay (single cell alkaline gel electrophoresis) (14) was applied to freshly isolated lymphocytes; >90% of cells were intact as indicated by the trypan blue test. Briefly, cells embedded in agarose on microscope slides were lysed to produce nucleoids, and electrophoresed in alkali. DNA loops containing breaks extend under electrophoresis to form ‘comet tails’, and the relative intensity of DNA in the tail indicates the DNA break frequency. Tail intensity was assessed by visual scoring; 100 comets selected at random were graded according to degree of damage into five classes (0–4) to give an overall score for each gel of between 0 and 400 arbitrary units. In addition to frank DNA strand breaks, oxidized bases were measured by conversion to breaks using endonuclease III (which recognizes oxidized pyrimidines) or formamidopyrimidine DNA glycosylase (FPG, specific for altered purines including formamidopyrimidines and 8-oxoGua). The enzyme 3-methyladenine DNA glycosylase II (AlkA) was used in a similar way to analyse DNA alkylation. Net enzyme-sensitive sites were calculated by subtracting the comet score after incubation with buffer alone from the score with enzyme. Results from the asbestos and stonewool groups have been published (12,13).
Measurement of DNA repair
The assay for OGG1 activity (15) measures the ability of a cell-free lymphocyte extract to incise substrate DNA containing 8-oxoGua. The substrate was prepared by treating HeLa cells with the photosensitizer Ro 19–8022 (Hoffmann La Roche, Basel, Switzerland) at 0.2 µM plus visible light (4 min irradiation on ice at 330 mm from a 1000 W tungsten halogen lamp). These cells were then embedded in agarose and lysed as for the standard comet assay. To prepare the lymphocyte extract, the snap-frozen samples were thawed, and lysis was completed by adding 12 µl of 1% Triton X-100. The lysate was centrifuged at 13 000x g for 5 min at 4°C. The supernatant was mixed with 4 vol. of 45 mM HEPES, 0.25 mM EDTA, 2% glycerol and 0.3 mg/ml bovine serum albumin, pH 7.8 and 40 µl aliquots were added to gels with substrate DNA and incubated for 10 min at 37°C. Alkaline treatment and electrophoresis followed as in the standard comet assay. The increase in DNA breaks at 10 min (relative to unincubated gels) was taken as the measure of repair incision for statistical analysis. Results from the asbestos and stonewool groups have been published previously (12,13).
DNA isolation and XPA genotyping
Genomic DNA was isolated from frozen peripheral blood samples collected into potassium-EDTA-containing tubes (Sarstedt, Nümbrecht, Germany), using these standard steps: lysis of erythrocytes (0.32 M sucrose, 1% Triton, 50 mM MgCl2 and 12 mM Tris, pH 12), lysis of lymphocytes (10% SDS, 5 M NaCl, buffer for proteinase K) followed by phenol–chloroform–isoamylalcohol extraction and ethanol precipitation.
The method for identifying the XPA polymorphism (rs1800975) was modified from ref. 7. Analysis of the XPA 23AG substitution in the nucleotide –4 from the ATG start codon was performed by restriction analysis of a 233 bp genomic PCR product. The following PCR primers within the 5'non-coding region were used: forward [XPA-(–4) F] 5'-TCA GAA AGG CCG CTG GGT-3'; and reverse [XPA-(–4) R] 5'-CTG GCG CAG CAT CAG TGC-3'.
Approximately 50 ng of DNA was used in a 25 µl PCR reaction containing: 1x PCR buffer [10 mM Tris–HCl (pH 8.8), 50 mM KCl and 0.1% Triton X-100], 2.5 mM MgCl2, 10% DMSO, 0.2 mM dNTP, 12.5 pmol of each primer and 1 U Taq polymerase DyNAzyme II (FINNZYMES, Espoo, Finland). The following thermal cycling conditions were performed in a thermocycler (PTC-0200; MJ Research, Watertown, USA): denaturation at 94°C for 5 min, followed by 35 cycles of denaturation (94°C for 30 s), annealing (58°C for 30 s) and elongation (72°C for 60 s), with the final cycle of elongation at 72°C for 7 min. Aliquots of 15 µl of the PCR product were then digested with 10 U MspI (New England Biolabs, Beverly, USA) for 6 h at 37°C in a total volume of 20 µl. The digestion products were separated by electrophoresis in 3% agarose gel. The A allele DNA was cut into two fragments (138 and 95 bp) and the G allele DNA into three fragments (108, 95 and 30 bp).
We selected 1 in 10 samples at random for repeated PCR–RFLP analysis and found 100% concordance.
Statistics
Correlation coefficients were calculated for relationships between two continuous variables. When normal distribution was rejected, then non-parametric Spearman correlation was used. For comparison of two groups, two-sample two-sided Student's t-test was used, or, when normal distribution was rejected, the two-sample two-sided Wilcoxon's test. For comparison of three groups, one-way analysis of variance and Bonferroni test (when equal variances were assumed) or Tamhane's test (when equal variances were not assumed) were used, or, when normal distribution was rejected, the Kruskal–Wallis test. Relationships between two discrete variables were assessed with the 
2-test in contingency tables.
Statistical models were based on multifactorial analysis of variance.
|
Results |
|---|
|
TopIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Association of XPA genotype with DNA base damage and repair
Frequencies of the different XPA alleles and of the three genotypes AA, AG and GG do not differ between the exposed and control groups, or between men and women (Table IA). They are in Hardy–Weinberg equilibrium. Table IB shows that, while strand breaks (SBs) were higher in exposed compared with control groups (all three factories combined), there was apparently no effect of exposure on the various kinds of DNA base damage. The data on DNA damage in the asbestos and stonewool factories were published previously (12
,13); data from the glass fibre factory are being prepared for publication.
|
Table II shows the mean levels of DNA damage and DNA repair in the different XPA genotypes. There is a significant association of the AA genotype with elevated FPG-sensitive sites in the whole study population, in combined control groups, in women and in non-smokers and in control women. Comparing probands with A allele (either AA or AG) with those homozygous for G also shows significant differences, particularly in levels of FPG-sensitive sites. Endonuclease III-sensitive and AlkA-sensitive sites showed similar patterns; endonuclease III-sites were significantly associated with the AA genotype in women and in the non-smokers, while AlkaA sites were higher in exposed subjects, in women and in the subgroup of exposed women. The same trend (i.e. higher DNA damage in subjects carrying the AA genotype) was seen in almost all subgroups. DNA repair was significantly higher in subjects with the AA genotype overall, and in the AA control group, in AA non-smokers and AA control women; a trend in the same direction was seen in most subgroups.
|
Separate analysis of subgroups of subjects in individual factories showed few strong associations, as the subgroups were too small for effects to be statistically significant. The association of FPG-sites with the AA genotype was significant in asbestos town controls (P = 0.03), endonuclease III-sites were associated with AA in men from the glass fibre factory (exposed and controls taken together) (P = 0.04), and OGG1 DNA repair activity was associated with AA genotype in non-smokers in the asbestos factory location and in the town controls (P = 0.04 and 0.02, respectively).
Associations of DNA damage with age
In the whole population, as well as in exposed subjects, there is a strong correlation of age with AlkA-sensitive, FPG-sensitive and endonuclease III-sensitive sites (Table III). Significant correlations are not seen in the control group (though they reappear when the men in the control group are analysed separately). The significant association of DNA base damage with age is seen in virtually all subgroups (men, women, smokers, non-smokers, exposed men, exposed women and control men). FPG-sites correlate with age in all stonewool factory controls (r = 0.39, n = 42, P = 0.01), and a borderline association is seen in all stonewool factory subjects (r = 0.15, n = 140, P = 0.07). A borderline association between endonuclease III-sites and age was found in asbestos exposed subjects (r = 0.25, n = 58, P = 0.06) and in all from the stonewool factory (r = 0.16, n = 141, P = 0.07).
|
Compared with base damage, SBs show less marked correlations with age; in the combined population (all three factories), correlations are seen in men, control men and non-smokers (Table III). Looking at individual factories, SBs correlate with age in all subjects from the asbestos monitoring study (r = 0.2, n = 129, P = 0.02) and in the asbestos-exposed group (r = 0.3, n = 61, P = 0.02).
A statistical model based on FPG-sites as dependent variable, with age and genotype as covariates, was highly significant (P < 0.0001). FPG-sites depend on genotype (P = 0.006). There was a relationship between age and FPG-sites (P = 0.001) and a significant interaction between FPG-sites and genotype (P = 0.02).
Association of OGG1 repair activity with age and genotype
Repair activity in lymphocytes shows a significant increase with age in the whole population (r = 0.1, n = 375, P = 0.04), as well as in all exposed subjects (r = 0.14, n = 239, P = 0.04). The correlation is not strong. When the whole population was divided according to age (
40, 41–60 and >60), the AA genotype was apparently more frequent in the oldest age group (Figure 1), but this is not statistically significant. However, the age-correlation is linked to genotype; a positive correlation with age is seen in the AA group overall and in women with the AA genotype (with a positive trend in non-smokers). A similar pattern of higher repair associated with age appears in groups with AG genotype, but, in GG individuals, there is no correlation with age (Table IV).
|
|
A statistical model confirms that repair is associated with age (P = 0.02).
|
Discussion |
|---|
|
TopIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
In our investigation of occupational exposure to asbestos (12
), we found an increase in oxidized pyrimidines (endonuclease III-sites) in the DNA of exposed men, but no increase in oxidized purines (FPG-sites). When the data from all three factories (asbestos, stonewool and glass fibre) were combined for the present study, there were no significant effects of exposure on DNA base damage (Table IB). However, SBs were significantly higher in exposed subjects in the stonewool study (13) and in the combined population (Table IB).
The number of subjects in the combined population is sufficiently large to investigate possible links between DNA base damage, repair of this damage and genetic susceptibility. Among the genes studied is XPA, in which, in three reports, a polymorphism is associated with lung cancer risk (8,9,11). Our markers of DNA damage and repair relate to BER rather than NER, and so the association between them and XPA polymorphisms (reported here) is unexpected. In the absence of a pre-existing hypothesis, it is particularly important to consider the possibility that this association has arisen by chance. The strategy that we have adopted is to maximize the chance of finding associations by first studying the population as a whole. The population is then divided into subgroups and the analysis repeated; only if the same associations appear as significant in subgroups do we regard them as reliable.
According to this criterion, the associations reported here between 8-oxoGua (FPG-sites) and OGG1 repair activity and XPA polymorphisms are particularly strong. The presence of one or two A alleles leads to significantly higher levels of FPG-sites in the whole population, the control group, men, non-smokers, control men and control women. The pattern of links between OGG1 activity and XPA genotype is similar, with significant associations in the whole population, in unexposed controls, in control women and in non-smokers.
The frequency of the 23AG polymorphism in our population is 60%. The A allele [sometimes referred to as wild-type (8)] is thus the less common allele, as was also reported by Butkiewicz et al. (11). According to the results of Wu et al. (9), the G allele gives the more efficient repair protein (at least as far as NER is concerned).
It is noteworthy that the AA genotype [linked with elevated cancer risk (8,9,11)] is associated with both a high level of FPG-sensitive sites and a high level of OGG1 DNA repair activity. FPG-sites are not exclusively 8-oxoGua, as FPG recognizes FaPy-residues (produced by ring-opening of damaged purines) in addition to 8-oxoGua (16). However, OGG1 has a similar substrate specificity (17), and so FPG-sensitive sites give a good indication of the level of oxidative damage present as a substrate for OGG1.
A hypothesis that would fit our observations is that XPA protein is involved in the repair of oxidative base damage. NER, and XPA protein in particular, might under certain circumstances act on damaged bases; in bacteria the UvrABC complex can repair oxidized purines when the DNA glycosylases are saturated or inactive (18). In that case, if the XPA product is relatively lacking (in abundance or activity) when the A allele is present, this might in turn lead to a higher steady state level of oxidized bases, as we observed. The accumulation of 8-oxoGua might then lead to a compensatory increase in the activity of OGG1 in the BER pathway. The problem with this hypothesis is that the role of XPA in NER is thought to be damage recognition or verification; it is unlikely that XPA has a dual role in the recognition of such distinct kinds of damage as UV-induced intra-strand cross-links on the one hand, and oxidized bases on the other.
A possible role for proteins from the NER pathway in so-called transcription-coupled repair of 8-oxoGua in mammalian cells has been proposed in several reports, but the reliability of the evidence is under intense scrutiny (19). The results we present here imply that there may in fact be an involvement of NER proteins (specifically XPA) in repair of 8-oxoGua, but the mechanism remains obscure.
In several cases (Table II, differences indicated by superscript letters), genotype seems to accentuate differences between controls and exposed, men and women, or smokers and non-smokers.
We found a weak (but significant) positive association between OGG1 repair activity and age. The generally accepted dogma is that repair activity should decline with age. However, experimental evidence for this is scarce, since reliable assays for repair that can be applied in population studies have only recently been available. The increase that we see here could be explained by an increase in the proportion of AA genotype with age, since DNA repair activity is higher in those with AA genotype. Such a shift was seen (Figure 1) but was not statistically significant. However, genotype does seem to have a significant influence; the association of OGG1 activity with age is stronger in those with AA or AG genotype. There is clearly a need for further investigation of this so far unexplained phenomenon.
|
Acknowledgments |
|---|
We are grateful to A. Horská and J. Ga
parovi
for their technical advice and support. We also thank A. Gaiová, A. Morávková, R. Mátéová and K. Burghardtová for their excellent technical help with analysis and evaluation of results. Z.D. received support from the EC FP5 Centre of Excellence QLK6-CT-2002-90445 to study polymorphisms in repair genes in the group of Professor Mieczyslaw Chorazy, Department of Tumor Biology, Centre of Oncology-M. Sklodowska-Curie Memorial Institute, Gliwice, Poland under the supervision of Drs Dorota Butkiewicz and Marek Rusin. The Fibretox project was supported by the European Commission (QLK4-CT-1999-01629) and the genotype analysis by a bilateral Slovak-Greek grant. We are grateful to Professor Soterios Kyrtopoulos for his co-ordination of Fibretox and joint co-ordination of the Slovak–Greek grant. |
Notes |
|---|
*To whom correspondence should be addressed. Tel: +421259369270; Fax: +421259369270; Email: maria.dusinska{at}szu.sk
|
References |
|---|
|
TopIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
-
1. Aboussekhra A., Biggerstaff M., Shivji M.K.K., Vilpo J.A., Moncollin V., Podust V.N., Protic M., Hübscher U., Egly J.-M., Wood R.D. (1995) Mammalian DNA nucleotide excision repair reconstituted with purified protein components. Cell 80:859–868.[CrossRef][ISI][Medline]
2. Tanaka K., Miura N., Satokata I., Miyamoto I., Yoshida M.C., Satoh Y., Kondo S., Yasui A., Okayama H., Okada Y. (1990) Analysis of a human DNA excision repair gene involved in group-A xeroderma-pigmentosum and containing a zinc-finger domain. Nature 348:73–76.[CrossRef][Medline]
3. Batty D.P. and Wood R.D. (2000) Damage recognition in nucleotide excision repair of DNA. Gene 241:193–204.[CrossRef][ISI][Medline]
4. Wakasugi M. and Sancar A. (1999) Order of assembly of human DNA repair excision nuclease. J. Biol. Chem. 274:18759–18768.
5. Sugasawa K., Ng J.M.Y., Masutani C., Iwai S., van der Spek P.J., Eker A.P.M., Hanaoka F., Bootsma D., Hoeijmakers J.H.J. (1998) Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol. Cell 2:223–232.[CrossRef][ISI][Medline]
6. Lehmann A.R. (2003) DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Biochimie 85:1101–1111.[Medline]
7. Butkiewicz D., Rusin M., Harris C.C., Chorazy M. (2000) Identification of four single nucleotide polymorphisms in DNA repair genes: XPA and XPB (ERCC3) in Polish population. Hum. Mutat. 15:577–578.[Medline]
8. Park J.Y., Park S.H., Choi J.E., et al. (2002) Polymorphisms of the DNA repair gene xeroderma pigmentosum group A and risk of primary lung cancer. Cancer Epidemiol. Biomarkers Prev. 11:993–997.
9. Wu X.F., Zhao H., Wei Q.Y., Amos C.I., Zhang K., Guo Z.Z., Qiao Y.Q., Hong W.K., Spitz M.R. (2003) XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity. Carcinogenesis 24:505–509.
10. Wei Q., Cheng L., Amos C.I., Wang L.E., Guo Z., Hong W.K., Spitz M.R. (2000) Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study. J. Natl Cancer Inst. 92:1764–1772.
11. Butkiewicz D., Popanda O., Risch A., Edler L., Dienemann H., Schulz V., Kayser K., Drings P., Bartsch H., Schmezer P. (2004) Association between the risk for lung adenocarcinoma and a (–4) G-to-A polymorphism in the XPA gene. Cancer Epidemiol. Biomarkers Prev. 13:2242–2246.
12. Dusinska M., Collins A., Kazimirova A., Barancokova M., Harrington V., Volkovova K., Staruchova M., Horska A., Wsolova L., Kocan A. (2004) Genotoxic effects of asbestos in humans. Mutat. Res. 553:91–102.[ISI][Medline]
13. Dusinska M., Barancokova M., Kazimirova A., Harrington V., Volkovova K., Staruchova M., Horska A., Wsolova L., Collins A. (2004) Does occupational exposure to mineral fibres cause DNA or chromosome damage? Mutat. Res. 553:103–110.[Medline]
14. Collins A.R. (2004) The comet assay for DNA damage and repair. Mol. Biotech. 26:249–261.[CrossRef][ISI][Medline]
15. Collins A.R., Dusinska M., Horvathova E., Munro E., Savio M., Stetina R. (2001) Inter-individual differences in DNA base excision repair activity measured in vitro with the comet assay. Mutagenesis 16:297–301.
16. Boiteux S., Gajewski E., Laval J., Dizdaroglu M. (1992) Substrate specificity of the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase): Excision of purine lesions in DNA produced by ionizing radiation or photosensitization. Biochemistry 31:106–110.[CrossRef][Medline]
17. Boiteux S. and Radicella J.P. (1999) Base excision repair of 8-hydroxyguanine protects DNA from endogenous oxidative stress. Biochimie 81:59–67.[Medline]
18. Boiteux S. (1993) Properties and biological functions of the NTH and FPG proteins of Escherichia coli: two DNA glycosylases that repair oxidative damage in DNA. J. Photochem. Photobiol. B: Biol. 19:87–96.[CrossRef][Medline]
19. Le Page F., Kwoh E.E., Avrutskaya A., Gentil A., Leadon A.A., Sarasin A., Cooper P.K. (2005) Transcription-coupled repair of 8-oxoGuanine: requirement for XPG, TFIIH, and CSB and implications for Cockayne syndrome (retraction). Cell 123:711.[Medline]
Received on December 20, 2005; revised on February 20, 2006; accepted on March 2, 2006.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Dusinska and A. R. Collins The comet assay in human biomonitoring: gene-environment interactions Mutagenesis, May 1, 2008; 23(3): 191 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Humphreys, R. M. Martin, B. Ratcliffe, S. Duthie, S. Wood, D. Gunnell, and A. R. Collins Age-related increases in DNA repair and antioxidant protection: A comparison of the Boyd Orr Cohort of elderly subjects with a younger population sample Age Ageing, September 1, 2007; 36(5): 521 - 526. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Vodicka, R. Stetina, V. Polakova, E. Tulupova, A. Naccarati, L. Vodickova, R. Kumar, M. Hanova, B. Pardini, J. Slyskova, et al. Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects Carcinogenesis, March 1, 2007; 28(3): 657 - 664. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||