Mutagenesis, Vol. 16, No. 6, 461-465,
November 2001
© 2001 UK Environmental Mutagen Society/Oxford University Press
Mutagenicity of a single 1-nitropyrene–DNA adduct N-(deoxyguanosin-8-yl)-1-aminopyrene in Escherichia coli located in a GGC sequence
Department of Chemistry, University of Connecticut, Storrs, CT 06269, USA
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and methodsResultsDiscussionReferences |
|---|
1-Nitropyrene, a common environmental pollutant, forms a major DNA adduct, N-(deoxyguanosin-8-yl)-1-amino- pyrene (dGAP). Mutational spectra of randomly introduced dGAP in Escherichia coli included different types of mutations, which depended on the base sequence surrounding the adduct. In earlier works we investigated the DNA sequence context effects of the adduct in repetitive CpG and non-repetitive CpGpC sequences. In the current work this adduct was incorporated into a non-repetitive GpGpC sequence in single-stranded M13mp7L2 DNA with the adduct located at either the 5' or 3' G. Potent genotoxicity of dGAP was evident from a significant reduction in the population of progeny phage following replication of these constructs in repair-competent E.coli cells. However, progeny derived from the 3'-GAP construct were much larger than those from the 5'-GAP construct. We suspect that a more facile translesion synthesis past the adduct at the 3' G relative to that at the 5' G, presumably due to a difference in conformation of dGAP in these two sites, might be responsible for this effect. With both adducted constructs, >95% of the progeny did not show any mutations at or near the adduct site, indicating highly efficient error-free translesion synthesis. However, a small population of mutants with one base deletions and base substitutions were detected. While the adduct induced –1 frameshifts (<1%) in each G site, base substitutions (1–2%), exhibiting predominantly G
C transversions, were detected only when the adduct was located at the 5' G. A comparison of the data from this study with a prior study in the CpGpC sequence suggests that dGAP mutagenesis is highly sensitive to the local DNA sequence and that a 5'-pyrimidine base might be important for targeted base substitutions by this adduct in E.coli. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
1-Nitropyrene (1-NP), a ubiquitous environmental carcinogen (Rosenkranz et al., 1980
; Rosenkranz and Mermelstein, 1983, 1985; Hirose et al., 1984; Ohnishi et al., 1985; Kinouchi et al., 1986; International Agency for Research on Cancer, 1989; El-Bayoumy, 1992), forms a covalent DNA adduct, N-(deoxyguanosin-8-yl)-1-aminopyrene (dGAP), at the C8 position of 2'-deoxyguanosine (Scheme 1) (Howard and Beland, 1982; Howard et al., 1983; Stanton et al., 1985). Two-dimensional NMR studies of duplex 11mers containing a dGAP show that the aminopyrene ring of the adduct is intercalated into the DNA helix between two intact Watson–Crick base pairs flanking the site, irrespective of whether a dC or dA was placed opposite dGAP (Mao et al., 1996; Gu et al., 1999). Intercalation of the aminopyrene ring results in displacement of the modified dG ring into the major groove. The glycosidic torsion angle of dGAP is in the syn domain. In each case, no hydrogen bond could be detected between the adducted dG and its partner.
|
Mutagenesis studies using randomly adducted DNA indicate that dGAP can induce both base substitution and frameshift mutations, although in bacteria the latter dominate the mutational spectrum (Stanton et al., 1988
; Bell et al., 1991; Melchoir et al., 1994; Malia and Basu, 1995). Frameshifts induced by dGAP include one base deletions, one base insertions and dinucleotide deletions. In order to determine the mechanism of mutagenesis by dGAP, we first constructed a single-stranded (ss) M13 genome in which the adduct was placed at the underlined deoxyguanosine of an inserted CGCGCG sequence (Malia et al., 1996). This DNA sequence was chosen because 1-NP is a very potent mutagen in Salmonella typhimurium frameshift tester strains (such as TA98) and induces CpG deletion in a repetitive CpG sequence near the reversion site (Bell et al., 1991). Using this site-specific construct, we found that dGAP induces nearly 2% CpG deletions in repair-competent Escherichia coli strains, which is 20-fold greater than that of the control (Malia et al., 1996). With SOS, the frequency of frameshift mutations is increased. The enhancement in mutation frequency (MF) is due to a +1 frameshift of either C or G residues adjacent to the adduct site. In a subsequent study, we investigated the mutagenicity of dGAP in a non-repetitive CGC DNA sequence (Bacolod et al., 2000). In this study one base deletions occurred only at the adjacent C residues, with a marked preference for deletion of the 3' C. The C deletions occurred at a frequency of 0.3–0.4% in uninduced cells, which increased 3- to 6-fold with SOS. Targeted GT and GC transversions were also detected at a frequency of ~2.2%. The base substitutions did not appear to be influenced by SOS. In the current investigation we have extended this work to a GGC sequence, in which dGAP mutagenesis was investigated at both the 5' and 3' G. This study, when compared with other single adduct mutagenesis, shows that DNA sequence context plays a major role in both the types and frequencies of dGAP mutagenesis.
|
Materials and methods |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Materials
Note that 1-NP and its derivatives are carcinogenic to rodents and should be handled carefully.
1-NP, 1-aminopyrene and m-chloroperoxybenzoic acid were obtained from Aldrich Chemical Co. (Milwaukee, WI). [
-32P]ATP was from Du Pont New England Nuclear (Boston, MA). T4 polynucleotide kinase and DNA ligase were obtained from New England Biolabs (Beverly, MA). Escherichia coli strains GW5100 (JM103, P1–) and DL7 (AB1157, lac
U169, uvr+), which carry a chromosomal lac deletion, have been reported previously (Malia and Basu, 1995).
Methods
Oligodeoxynucleotides were synthesized on an Applied Biosystems Model 380B DNA synthesizer, using the phosphoramidite method. HPLC separations were performed using reversed phase columns (Phenomenex C-18, 5 µm particle size, 4.6x250 mm). The 11mer containing dGAP was synthesized as reported (Vyas et al., 1993; Nolan et al., 1999). All M13 minipreps were done using Qiagen Spin M13 Kits (Qiagen, Valencia, CA). DNA sequencing reactions were performed using Big Dye Terminator Cycle Sequencing Ready Reactions from PE Applied Biosystems (Foster City, CA). The sequencing runs were carried out in an ABI Prism 377XL DNA Sequencer at the University of Connecticut Biotechnology Center (Storrs, CT).
Construction of site-specifically modified M13 genomes
Scheme 2 shows the steps for construction of site-specifically modified ss M13 genomes and the subsequent assay for mutagenesis. Bacteriophage M13mp7L2 DNA (400 µg) was digested with EcoRI (3200 U) for 2 h at 25°C in 1 ml of 100 mM Tris–HCl, pH 7.5, 5 mM MgCl2 and 50 mM NaCl. Agarose gel electrophoresis indicated no visible band for the remaining circular DNA. An equimolar ratio of a scaffold 50mer was annealed to the linear ssDNA at a concentration of 100 ng/ml by heating at 75°C for 15 min followed by slow cooling to room temperature over a period of 3–4 h. A 10-fold molar excess of the modified or unmodified 5'-phosphorylated 11mer was ligated into the gap of this annealed DNA in the presence of 800 U T4 DNA ligase in 40 mM Tris–HCl buffer, pH 7.8, 8 mM MgCl2, 16 mM dithiothreitol and 1 mM ATP at 16°C for 48 h. After ethanol precipitation, an additional round of EcoRI (5 U/µg DNA) digestion was carried out for 4 h to linearize any uncut or religated DNA. To remove the 50mer scaffold from the M13 DNA, each DNA solution was heated at 100°C for 45 s and rapidly cooled to 0°C. Prior to heating, a 10-fold molar excess of an `anti-scaffold' 50mer that contained the DNA sequence complementary to the scaffold oligomer was added to prevent the scaffold from reannealing on the M13 DNA (Ramos et al., 1998). To monitor whether removal of the scaffold was quantitative, an aliquot of gapped circular M13 DNA was subjected to the same steps of denaturation and analyzed by agarose gel electrophoresis. The ligation efficiency was determined by comparing the slower running circular DNA band with the faster running linear DNA with the aid of a Kodak Digital Science Electrophoresis Documentation and Analysis System 120 and 1D Image Analysis Software.
|
SOS induction and transformation in E.coli
Repair-competent E.coli (DL7) cells were grown in 100 ml cultures in Luria broth to 1x108 cells/ml and then harvested by centrifugation at 5000 g for 15 min at 0°C. The cells were resuspended in an equal volume of ice-cold deionized water and recentrifuged at 5000 g for 30 min. This procedure was repeated, except that the cells were resuspended in 50 ml of ice-cold deionized water. The bacterial pellet was resuspended in 1 ml of glycerol/water (10% v/v) and kept on ice until further use. To induce SOS, the following additional steps were introduced after the first centrifugation. The cells were resuspended in 50 ml of 10 mM MgSO4 and treated with 20 J/m2 UV light (254 nm) in 25 ml aliquots in 150x50 mm plastic Petri dishes. The cultures were incubated in Luria broth at 37°C for 40 min in order to express SOS functions maximally. Following SOS induction, these cells were centrifuged, deionized and resuspended in glycerol/water in a similar manner as described above, except that all manipulations were carried out in subdued light.
For each transformation, an aliquot (60 µl) of the cell suspension was mixed with 60 ng M13 construct and transferred to the bottom of an ice-cold Bio-Rad Gene Pulser cuvette (0.1 cm electrode gap). Electroporation of cells was carried out in a Bio-Rad Gene Pulser apparatus at 25 µF and 1.8 kV with the pulse controller set at 200 
. Immediately after electroporation, 1 ml of SOC medium (Sambrook et al., 1989) was added and the mixture was transferred to a 1.5 ml microcentrifuge tube. Following a 1 h recovery at 37°C, the cells were centrifuged at 15 000 g for 5 min to isolate the phage-containing supernatant.
Each M13 construct generated after ligation of the 11mer is a +1 derivative of M13mp7, which gave clear plaques in the presence of IPTG and X-gal. A –1 (or +2) frameshift should restore the reading frame, resulting in blue plaques. We used this phenotypic screening to identify the putative one base deletion mutants. Progeny phage that produced clear plaques in the presence of IPTG and X-gal were analyzed by a differential oligonucleotide hybridization technique, as reported (Bacolod et al., 2000).
|
Results |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Construction of M13 genomes
The adducted 11mers 5'-CCATGAP5G6C7TACC-3' and 5'-CCATG5GAP6C7TACC-3 were synthesized by reacting N-hydroxy-1-aminopyrene (NHOP) generated in situ from 1-nitrosopyrene in DMF/sodium acetate buffer, pH 5.0, in the presence of ascorbic acid as reported (Vyas et al., 1993
). The reversed phase HPLC profile of the reaction mixture, subsequent to extraction of unreacted NHOP, showed two additional peaks running more slowly than the unmodified 11mer (Figure 1). Polyacrylamide gel electrophoresis of these two modified oligonucleotides, following purification and 32P-radiolabeling, showed slower mobility than the unmodified 11mer, as expected. Piperidine cleavage followed by PAGE (as described in Malia et al., 1996) established that the peak eluting at 19.7 min contained the 11mer with the adduct at the 5' G (i.e., ...GAP5G6C7...), whereas the 20.6 min peak contained the 11mer with the adduct at the 3' G (i.e., ...G5GAP6C7...).
|
The construction of site-specifically modified M13 genomes was accomplished by a strategy originally developed by Lawrence and co-workers (Banerjee et al., 1988
), which is routinely used in our laboratory (Scheme 2
) (Malia et al., 1996; Hanrahan et al., 1997; Ramos et al., 1998; Bacolod et al., 2000). The 5'-phosphorylated control and adducted 11mers were ligated to a gapped M13mp7L2 DNA. Prior to ligation, both adducted and control 11mers were examined for purity. As indicated earlier, the mobility of the adducted 11mer was significantly retarded with respect to that of the control 11mer (Figure 2), which allowed analysis with a phosphorimager to ensure that each 11mer was >99.6% pure. Ligation efficiency, which was typically 25 ± 5% for both control and adducted DNA, was determined by running a portion of the constructs on an agarose gel followed by densitometry analysis and, based on the ligation efficiency, the same amount of circular genome was used for transformations.
|
Viability of the site-specifically modified M13 genomes
A single dGAP reduced viability of the M13 genome, as noted in other studies (Table I
) (Malia et al., 1996; Bacolod et al., 2000). The viabilities of the constructs containing dGAP at two adjacent sites were quite different (Table I). In the absence of SOS, the number of progeny with the adduct at G5 was only 0.8 ± 0.3%, compared with 24 ± 12% when the adduct was at G6. Unfortunately, a meaningful comparison of the survival data could not be carried out because with the GAP5 construct in SOS-induced cells, particularly when the transformation efficiency was less than optimal, variation in viability of up to two orders of magnitude was observed between experiments. Nevertheless, a difference in viability owing to the location of the adduct at the two sites was evident. This was not completely unexpected, since efficiencies of translesion synthesis past other bulky adducts, such as the C8 guanine adduct of N-acetyl-2-aminofluorene and the N2 guanine adduct of (+)-anti-benzo[a]pyrene diol epoxide have been shown to vary depending on the bases flanking the lesion (Burnouf et al., 1999; Zhuang et al., 2001). The molecular basis for such differences in translesion synthesis is not clearly understood, but the conformation of the adduct in the particular sequence context has been suspected to play a role (Zhuang et al., 2001). Further investigation will be necessary to confirm the differences in viability and to elucidate the mechanism of this process.
|
Frameshift mutagenesis
Sequencing of the DNA isolated from the blue plaques revealed that one base deletions occurred at either one of the G or the 3' C (i.e., C7) residue (Table II
). It is noteworthy that C7 deletions occurred even when the adduct was located at G5. When the adduct was at G5 one base deletions occurred at an average frequency of 0.4%, which did not increase with SOS (Table II). The –1 deletion frequencies were 0.5 and 0.8% without and with SOS, respectively, when the adduct was located at G6. In a prior study in which the local sequence CGAPC was used, –1 deletions occurred at the adjacent C residues with a marked preference for deletion of the 3' C. In the current study, in contrast, G deletions were predominant. Because of a G residue adjacent to the adduct, however, we could not determine if the G deletions were targeted.
|
Mutational analysis of progeny by oligonucleotide hybridization
To investigate base substitutions and other types of frameshifts, we employed oligonucleotide hybridization using a 17mer probe complementary to the region of M13 where the 11mer was inserted. The probe was designed to bind only to the non-mutant plaques. Therefore, all non-hybridized or weakly hybridized plaques were considered putative mutants and subjected to DNA sequencing. As shown in Table III
, base substitutions could only be detected when the adduct was at G5. The adduct at this site induced 1–2% base substitutions, which primarily consisted of GC transversions. Induction of SOS did not appear to influence the base substitutions, as was also observed in the prior study in the CGAPC sequence (Bacolod et al., 2000). The average frequency of base substitution at G5 was not significantly different when the adduct was located at G6 but with a C immediately 5' to it (Bacolod et al., 2000). The total mutation frequency, including both frameshifts and base substitutions in both SOS-induced and uninduced cells, therefore increased to ~2% for GAP5, whereas the frequency remained unaltered at ~0.6% for GAP6. It was indeed surprising that the adduct at G6 did not show any base substitutions. Another notable difference in the current study is that GC was the predominant (>70%) type of base substitution (Table III), whereas both GC and GT transversions occurred at significant frequency in the CGAPC sequence (Bacolod et al., 2000). No mutants were detected from the control construct after screening more than 3000 plaques derived from four separate transformations of uninduced and SOS-induced cells (Table III).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
The present study clearly demonstrates that mutagenesis of dGAP is highly dependent on the DNA sequence context. In our first site-specific study, using a repetitive CpG sequence, single base deletions and base substitutions were not detected (Malia et al., 1996
), even though mutational spectra of reductively activated 1-nitropyrene included base substitutions and –1 and +1 frameshifts (Stanton et al., 1988; Melchoir et al., 1994; Malia and Basu, 1995). This work was followed by another site-specific study with the adduct located in a non-repetitive CGC sequence (Bacolod et al., 2000). In contrast to the dinucleotide deletions and one base insertions in the repetitive CpG sequence, the adduct induced one base deletions of the adjacent C residues and targeted base substitutions in the non-repetitive CpGpC sequence. The effect of SOS is also noteworthy in that C deletions increased 3- to 6-fold, whereas the frequency of base substitutions remained approximately the same. It is interesting in the current study that when the immediate 5' C was replaced with a G, base substitutions could not be detected at G6. We speculate that a 5' pyrimidine base may be important for base substitutions by dGAP, since GC substitutions occurred when the adduct was at G5, with a T immediately 5' to it. However, in the prior study in a CGAPC sequence ~70% of the base substitutions were GT transversions. In contrast, in the current TGAPGC sequence >70% of the base substitutions were GC and only 13% were GT events. It is conceivable that a change in local DNA sequence may change the conformation of the adduct, which in turn alters the mutagenic specificity. In the mutational spectrum of randomly introduced dGAP in M13 ssDNA GC substitutions were rare and only 3 of 149 events were detected (Malia and Basu, 1995). It is noteworthy, however, that in this study the frequency of GC substitutions with and without SOS remained the same, while GA and GT substitutions and frameshifts increased significantly with SOS (Malia and Basu, 1995). The lack of increased base substitution by SOS in the current work, therefore, is not inconsistent with the random mutagenesis study. We suspect that the adduct in this ...TGAPGC... sequence can occasionally induce GC substitutions by a SOS-independent pathway. In contrast, in the TGGAPC sequence the same adduct might pair more efficiently with C, resulting not only in increased translesion synthesis but also in lesion bypass without detectable base substitution. In the random mutagenesis study G deletions were common in several TGGC sites, but none of the GC events occurred in these sites (Malia and Basu, 1995). Since sequence context effects in adduct-induced mutagenesis go beyond the immediate neighbors, such apparent anomalies are not surprising.
For the one base deletions, stalling of the DNA polymerase at or near the adduct site probably allows slippage to occur. For example, one base deletions occurred in each of the sequences C5G6APC7, G5G6APC7 and G5APG6C7. In an earlier site-specific study of the C8 guanine adduct of N-acetyl-2-aminofluorene, plasmids containing the adduct in each G of the contiguous run of guanines G1G2G3 were constructed (Lambert et al., 1992). Upon replication of the constructs in SOS-induced cells, one base deletions with the adduct at G3 were found to be 100- and 10-fold greater than when it was located at G2 and G1, respectively. In another study one base deletions by the randomly introduced C8 guanine adduct of 1-nitroso-6-nitropyrene increased nearly an order of magnitude when two consecutive G sites were compared with an isolated G (Lambert et al., 1998). In the current study of dGAP in SOS-induced cells, although one base deletions at G6 occurred at an average frequency of 0.8% compared with 0.3% at G5, the difference was clearly not as pronounced. It is unclear whether this was the result of this particular sequence. It is noteworthy that despite the lack of hydrogen bonding and an antisyn base rotation, which were shown in solution NMR studies (Mao et al., 1996; Gu et al., 1999), translesion bypass past dGAP occurs accurately in >95% of the progeny. We find such fidelity particularly remarkable in ssDNA, where the adduct cannot be repaired by most known DNA repair systems.
|
Acknowledgments |
|---|
This work was supported by grant ES09127 from the National Institute of Environmental Health Sciences, NIH. A.K.B. is the recipient of a Research Career Development Award (K02 ES00318) from the NIEHS.
|
Notes |
|---|
1 To whom correspondence should be addressed: Tel: +1 860 486 3965; Fax: +1 860 486 2981; Email: ashis.basu{at}uconn.edu
|
References |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
-
Bacolod,M.D., Krishnasamy,R. and Basu,A.K. (2000) Mutagenesis of N-(deoxyguanosin-8-yl)-1-aminopyrene in a nonrepetitive CGC sequence in Escherichia coli. Chem. Res. Toxicol., 13, 523–528.[Web of Science][Medline]
Banerjee,S.K., Christensen,R.B., Lawrence,C.W. and LeClerc,J.E. (1988) Frequency and spectrum of mutations produced by a single cis-syn thymine-thymine cylobutane dimer in a single-stranded vector. Proc. Natl Acad. Sci. USA, 85, 8141–8145.
Bell,D.A., Levine,J.G. and DeMarini,D.M. (1991) DNA sequence analysis of revertants of the hisD3052 allele of Salmonella typhimurium TA98 using the polymerase chain reaction and direct sequencing: application to 1-nitropyrene-induced revertants. Mutat. Res., 252, 35–44.[Web of Science][Medline]
Burnouf,D.Y., Miturski,R. and Fuchs,R.P.P. (1999) Sequence context modulation of translesion synthesis at a single N-2-acetylaminofluorene adduct located within a mutation hot spot. Chem. Res. Toxicol., 12, 144–150.[Web of Science][Medline]
El-Bayoumy,K. (1992) Environmental carcinogens that may be involved in human breast cancer etiology. Chem. Res. Toxicol., 5, 585–590.[Web of Science][Medline]
Gu,Z., Gorin,A., Krishnasamy,R., Hingerty,B.E., Basu,A.K., Broyde,S. and Patel,D.J. (1999) Solution structure of the N-(deoxyguanosin-8-yl)-1-aminopyrene ([AP]dG) adduct opposite dA in a DNA duplex. Biochemistry, 38, 10843–10854.[Medline]
Hanrahan,C.J., Bacolod,M.D., Vyas,R.R., Liu,T.-M., Geacintov,N.E., Loechler,E.L. and Basu,A.K. (1997) Sequence specific mutagenesis of the major (+)-anti-benzo(a)pyrene diol epoxide-DNA adduct at a mutational hotspot in vitro and in Escherichia coli cells. Chem. Res. Toxicol., 10, 369–377.[Web of Science][Medline]
Hirose,M., Lee,M.-S., Wang,C.Y. and King,C.M. (1984) Induction of rat mammary gland tumors by 1-nitropyrene, a recently recognized environmental mutagen. Cancer Res., 44, 1158–1162.
Howard,P.C. and Beland,F.A. (1982) Xanthine oxidase catalyzed binding of 1-nitropyrene to DNA. Biochem. Biophys. Res. Commun., 104, 727–732.[Web of Science][Medline]
Howard,P.C, Heflich,R.H., Evans,F.E. and Beland,F.A. (1983) Formation of DNA adducts in vitro and in Salmonella typhimurium upon metabolic reduction of the environmental mutagen 1-nitropyrene. Cancer Res., 43, 2052–2058.
International Agency for Research on Cancer (1989) IARC Monographs on the Evaluation of Carcinogenic Risk to Humans, Vol. 39, The Genotoxicity, Metabolism and Carcinogenicity of Nitrated Polycyclic Hydrocarbons. IARC, Lyon, pp. 1–458.
Kinouchi,T., Tsutsui,H. and Ohnishi,Y. (1986) Detection of 1-nitropyrene in yakitori (grilled chicken). Mutat. Res., 171, 105–113.[Web of Science][Medline]
Lambert,I.B., Napolitano,R. and Fuchs,R.P.P. (1992) Carcinogen-induced frameshift mutagenesis in repetitive sequences. Proc. Natl Acad. Sci. USA, 89, 1310–1314.
Lambert,I.B., Carroll,C., Laycock,N., Duval,L., Whiteway,J., Lawford,I., Turner,G., Booth,R., Douville,S. and Nokhbeh,M.R. (1998) The mutational specificity of 1-nitroso-6-nitropyrene in the lacI gene of Escherichia coli strains deficient in nucleotide excision repair. Mutagenesis, 13, 9–18.
Malia,S.A. and Basu,A.K. (1995) Mutagenic specificity of reductively activated 1-nitropyrene in Escherichia coli. Biochemistry, 34, 96–104.[Medline]
Malia,S.A., Vyas,R.R. and Basu,A.K. (1996) Site-specific frame-shift mutagenesis by the 1-nitropyrene-DNA adduct N-(deoxyguanosin-8-yl)-1-aminopyrene located in the (CG)3 sequence: effects of SOS, proofreading and mismatch repair. Biochemistry, 35, 4568–4577.[Medline]
Mao,B., Vyas,R.R., Hingerty,B.E., Broyde,S., Basu,A.K. and Patel,D.J. (1996) Solution conformation of N-(deoxyguanosin-8-yl)-1-aminopyrene opposite dC in a DNA duplex. Biochemistry, 35, 12659–12670.[Medline]
Melchoir,W.B.Jr, Marques,M.M. and Beland,F.A. (1994) Mutations induced by aromatic amine DNA adducts in pBR322. Carcinogenesis, 15, 889–899.
Nolan,S.J., McNulty,J.M., Krishnasamy,R., McGregor,W.G. and Basu,A.K. (1999) C8-guanine adduct-induced stabilization of a –1 frameshift intermediate in a nonrepetitive DNA sequence. Biochemistry, 38, 14056–14062.[Medline]
Ohnishi,Y., Kinouchi,T., Manabe,Y., Tsutsui, Otsuka,H., Tokiwa,H. and Otofuji,T. (1985) Nitro compounds in environmental mixtures and foods. In Waters,M.D., Shandhu,S.S., Lewtas,J., Claxton,L., Strauss,G. and Nesnow,S. (eds) Short Term Genetic Bioassays in the Evaluation of Complex Environmental Mixtures. Plenum Press, New York, NY, pp. 195–204.
Ramos,L.A., Lipman,R., Tomasz,M. and Basu,A.K. (1998) The major mitomycin C-DNA monoadduct is cytotoxic but not mutagenic in Escherichia coli. Chem. Res. Toxicol., 11, 64–69.[Web of Science][Medline]
Rosenkranz,H.S. and Mermelstein,R. (1983) Mutagenicity and genotoxicity of nitroarenes. All nitro-containing chemicals were not created equal. Mutat. Res., 114, 217–267.[Web of Science][Medline]
Rosenkranz,H.S. and Mermelstein,R. (1985) The genotoxicity, metabolism and carcinogenicity of nitrated polycyclic hydrocarbons. J. Environ. Sci. Health, C3, 221–272.
Rosenkranz,H.S., McCoy,E.C., Sanders,D.R., Butler,M., Kiriazides,D.K. and Mermelstein,R. (1980) Nitropyrenes: isolation, identification and reduction of mutagenic impurities in carbon black and toners. Science, 209, 1039–1043.
Sambrook,J., Fritsch,E.F. and Maniatis,T. (1989) Molecular Cloning: A Laboratory Manual, 2nd Edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Stanton,C.A., Chow,F.L., Phillips,D.H., Grover,P.L., Garner,R.C. and Martin,C.N. (1985) Evidence for N-(deoxyguanosin-8-yl)-1-aminopyrene as a major DNA adduct in female rats treated with 1-nitropyrene. Carcinogenesis, 6, 535–538.
Stanton,C.A., Garner,R.C. and Martin,C.N. (1988) The mutagenicity and DNA base sequence changes induced by 1-nitroso- and 1-nitropyrene in the cI gene of lambda prophage. Carcinogenesis, 9, 1153–1157.
Vyas,R.R., Nolan,S.J. and Basu,A.K. (1993) Synthesis and characterization of oligodeoxynucleotides containing N-(deoxyguanosin-8-yl)-1-aminopyrene. Tetrahedron Lett., 34, 2247–2250.
Zhuang,P., Kolbanovskiy,A., Amin,S. and Geacintov,N.E, (2001) Base sequence dependence of in vitro translesional DNA replication past a bulky lesion catalyzed by the exo– Klenow fragment of pol I. Biochemistry, 40, 6660–6669.[Medline]
Received on March 26, 2001; accepted on June 25, 2001.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Hilario, S. Yan, B. E. Hingerty, S. Broyde, and A. K. Basu Comparative Mutagenesis of the C8-Guanine Adducts of 1-Nitropyrene and 1,6- and 1,8-Dinitropyrene in a CpG Repeat Sequence. A SLIPPED FRAMESHIFT INTERMEDIATE MODEL FOR DINUCLEOTIDE DELETION J. Biol. Chem., November 15, 2002; 277(47): 45068 - 45074. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||