Mutagenesis, Vol. 17, No. 1, 1-8,
January 2002
© 2002 UK Environmental Mutagen Society/Oxford University Press
Inducible protective processes in animal systems. X. Influence of nicotinamide in methyl methanesulfonate-adapted mouse bone marrow cells
1 Department of Zoology, 2 Department of Sericulture and 3 Department of Biochemistry, Manasagangotri, University of Mysore, Mysore-570 006, Karnataka State, India and 4 Department of Applied Zoology, Jnanasahyadri, Kuvempu University, BR Project-577 115, Shimoga District, Karnataka State, India
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Abstract |
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The adaptive response is an error-free DNA repair mechanism induced by low levels of physical or chemical agents. Cells pre-exposed to such agents are resistant to genetic damage induced by subsequent treatment at a high dose. There are many reports on such adaptive responses. Recently we have shown the existence of adaptive responses in vivo in the grasshopper Poecilocerus pictus and the mouse and in vitro in human lymphocytes. Different enzymes are implicated in this DNA repair pathway. In an attempt to understand the molecular mechanism of the methyl methanesulfonate (MMS)-induced adaptive response, the present investigations have been undertaken employing nicotinamide, an inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP). Pre-, inter- and post-treatments with nicotinamide of MMS-treated mouse bone marrow cells were carried out. The results revealed that there is a significant reduction in the frequency of chromosomal aberrations compared with combined treatment, suggesting an enhancement of the adaptive response by nicotinamide. Further, the results of NAD+ assay in the inter-treatment experiment showed that there is no depletion of NAD+. Thus, it can be stated that PARP is not involved in the MMS-induced adaptive response in mouse bone marrow cells.
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Introduction |
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TopAbstractIntroductionMaterials and methodsResults and discussionReferences |
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The ability of organisms, including man, to resist the DNA-damaging stress of environmental agents is dependent on detoxification and DNA repair pathways. The adaptive response or inducible DNA repair pathway is one such repair process, wherein cells pre-exposed to a low dose of a clastogen are resistant to the damaging effects of a high dose of the same agent. The discovery of this adaptive response by Samson and Cairns (1977) in Escherichia coli has lead to extensive research on understanding such processes in prokaryotes and in vitro eukaryotes using physical agents (Olivieri et al., 1984
; Shadley and Wolff, 1987; Sankaranarayanan, 1989; Liazhen Zhang, 1995; Ikushima et al., 1996; Wolff, 1996; Lankinen and Vilpo, 1997; Nikolai et al., 1998) and chemicals (Samson and Schwartz, 1980; Kaina, 1982; Olivieri and Bosi, 1990; Mudrigal-Bujaidar et al., 1994; Kleczkowska and Althaus, 1996; Nikolova and Huttner, 1996). Reports are available on the existence of such a phenomenon in higher plants using alkylating and non-alkylating agents (Rieger et al., 1982, 1990; Baranczewski et al., 1997). Recently we have also reported the existence of such inducible protective processes in in vivo animal systems such as the grasshopper Poecilocerus pictus and mouse (Riaz Mahmood and Vasudev, 1990, 1991, 1992, 1993; Riaz Mahmood et al., 1996; Vasudev et al., 1997; Harish et al., 2000; Guruprasad and Vasudev, 2001) and in vitro in human lymphocytes (Harish et al., 1998). Even though there are large amounts of data on the adaptive response, the molecular mechanism still remains elusive. Many repair enzymes are implicated in DNA repair processes. The study of these enzymes, related to the induction of the repair process in response to low levels of chemicals, might shed new light on the possible mechanism of the adaptive response. Poly(ADP-ribose) polymerase (PARP) is one such repair enzyme reported to participate in DNA repair and it has been shown that this enzyme regulates the activity of proteins such as histones, topoisomerases, DNA and RNA polymerases, DNA ligases and Ca2+/Mg2+-dependent endonucleases (Cohen and Duke, 1984; Althaus and Richter, 1987). PARP is activated by DNA strand breaks induced by alkylating agents (Cleaver et al., 1985; Chatterjee and Berger, 1994; Kleczkowska and Althaus, 1996). Upon activation PARP transfers monomers of ADP-ribose from NAD+ to chromatin-associated proteins or to other molecules of ADP-ribose to form a polymer. When activated, PARP depletes NAD+ and consequently ATP energy stores, resulting in cell death (see Cosi et al., 1996). Inhibitors of this enzyme have been shown to protect cells from the toxic effects of damaging agents (Cosi et al., 1994, 1996; Cosi and Marien, 1998; Chatterjee et al., 1999; Kolb and Burkart, 1999). In addition, inhibitors of this enzyme prevent adaptation in in vitro systems when applied during a 2 h period immediately after the adaptive treatment (Wiencke et al., 1986; Shadley and Wolff, 1987), suggesting its involvement in the adaptive response. Information on the involvement of PARP in the adaptive response in in vivo systems is not available. Hence, the present investigations were undertaken to increase our understanding of the role of this enzyme in the methyl methanesulfonate (MMS)-induced adaptive response in in vivo mouse bone marrow cells using nicotinamide, an inhibitor of PARP, the results of which are presented in this communication.
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Materials and methods |
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Animals
Male swiss albino mice aged 6–8 weeks and weighing 25–30 g were employed in the present studies. To overcome the influence of variation in the weight of animals on production of chromosomal aberrations by the chemical agents, same weight (28 g) animals were employed in one set of experiments. The animals were reared in the animal house of the Department of Zoology, providing appropriate environmental conditions such as temperature and humidity. The animals were maintained in polypropylene shoe box type cages with a grill top. Paddy husk was used as the bedding material. Utmost care was taken to maintain good cage hygiene and also to provide good ventilation and aeration in the animal room. The animals were provided with standard diet and water ad libitum.
Chemicals
The monofunctional alkylating agent MMS (CAS no. 66-27-3) and nicotinamide (CAS no. 98-92-0) were obtained from Sigma Chemical Co. (St Louis, MO). MMS and nicotinamide were dissolved in 0.7% NaCl and distilled water, respectively, to obtain the required concentrations. An aliquot of 0.5 ml of a fixed concentration was injected i.p. Freshly prepared solutions of these agents were used each time. The conditioning and challenging concentrations of MMS were established in previous experiments with mice (Riaz Mahmood et al., 1996) in which concentrations of 50 and 125 mg/kg body wt MMS as conditioning (L) and challenging (H) doses, respectively, were used. From the pilot toxicity experiments 600 mg/kg body wt (5 mM/kg body wt) nicotinamide was selected as it induced no toxic effects when given in a combined treatment (Table I). Mitotic index was calculated following the procedure of Madhuri Jaju (1982). To evaluate the lethality of nicotinamide and determine mitotic indices, 12 animals were used at each dose level. Three such experiments were conducted for each dose level. Thus a total of 36 animals were used to evaluate the extent of lethality and determine mitotic indices for each dose level.
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Treatment schedule
MMS combined treatment. This treatment regimen was again selected from previous experiments by the authors (Riaz Mahmood et al., 1996), who have shown that an 8 h time lag (TL) between the conditioning and challenging treatment offered maximum protection with respect to chromosomal aberrations in mouse bone marrow cells. Hence, for the present studies 8 h TL was selected.
Nicotinamide inter-treatment. A nicotinamide inter-treatment was made between the conditioning and challenging doses. As an 8 h TL was found to produce peak action or repair (Riaz Mahmood et al., 1996), this TL was selected. Nicotinamide was injected 2 or 4 h after the conditioning dose. Then, 6 or 4 h later the challenge dose of MMS was applied.
Nicotinamide pretreatment. In these experiments animals received nicotinamide 4 or 6 h before the conditioning dose of MMS and 8 h after the conditioning dose they were challenged with the same agent.
Nicotinamide post-treatment. Nicotinamide was given 6, 12 or 18 h after combined treatment with MMS.
Slide preparation and chromosome analysis
Animals were killed at 24, 48 or 72 h recovery times after the challenge dose by cervical dislocation. The bone marrow was processed and slides were prepared by the regular air drying technique (Evans et al., 1964). Coded Giemsa stained slides were screened for the presence of chromosome aberrations. Four independent experiments (A, B, C and D) with animals weighing 25–30 g and one experiment (E) with animals weighing 28 g were conducted in each series. For each experiment three animals were employed and all survived. The results were subjected to statistical analysis employing the one-tailed Student's t-test.
NAD+assay
NAD+ estimation in mouse liver cells was carried out following the modified procedure of Klingenberg (1975). The liver from inter-treatment and control animals was dissected out and 1 g of liver was homogenized in 5 ml of perchloric acid at 0°C. The samples were centrifuged at 4000 g. A sample of 1 ml of supernatant was removed and 0.2 ml of 0.1 N K2HPO4 was added. Then 3 N KOH was added with intensive stirring until the pH was 7.2–7.4. The KClO4 was allowed to sediment. To 1 ml of supernatant was added 1 ml of sodium pyrophosphate buffer and 0.01 ml of ethanol and these were well mixed. Quantification was by spectrophotometry (wavelength 340 nm) after 15 min. The first reading (E1) was taken after achieving a constant OD value. ADH (0.01 ml) was added and thoroughly mixed in. Reading E2 was taken 6 min later at the same wavelength. 
E = E2 – E1 is used in the calculations.
The quantity of NAD in the cell was calculated using
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is the extinction coefficient for NADH (6.22 cm2/µmol at 340 nm), V1 is the volume of the sample = weight/density, V2 is the volume (ml) of HClO4 required for deproteinization, V3 is the supernatant fluid (ml) removed after deproteinization, V4 is the volume (ml) of K2HPO4 solution added and V5 is the volume (ml) of KOH required for neutralization. The content per g fresh wt is found by taking into account the density p of the tissue.
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Results and discussion |
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The results obtained after pre-, post and inter-treatment of MMS-challenged mouse bone marrow cells with nicotinamide are presented in Tables II–IV
that MMS induces significant chromosomal aberrations (P < 0.05). This is on a par with the known mutagenicity and clastogenicity of MMS (Vogel and Natarajan, 1982). The chromosomal aberrations induced by MMS were mainly chromatid breaks, exchanges, intrachromatid deletions and minutes, i.e. chromatid-type aberrations, and were produced at all recovery times tested. These results are similar to earlier observations (Riaz Mahmood and Vasudev, 1993; Riaz Mahmood et al., 1996). Both the conditioning and challenging doses of MMS induced chromosomal aberrations at significantly higher levels compared with controls. On the other hand, the combined treatment (conditioning dose-8 h-challenge dose) produced significantly fewer chromosomal aberrations compared with the challenge treatment. This is in conformity with the results of earlier experiments by the authors (Riaz Mahmood et al., 1996). In addition, these results are also on a par with the results of previous reports on the adaptive response induced by chemicals (Samson and Schwartz, 1980; Kaina, 1982; Olivieri and Bosi, 1990; Mudrigal-Bujaidar et al., 1994; Kleczkowska and Althaus, 1996; Nikolova and Huttner, 1996).
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Wiencke (1987), while studying the influence of nicotinamide, an inhibitor of PARP, on the adaptive response, stated `ADPRT itself and not other metabolic processes affected by inhibitors of this enzyme, plays an important role in adaptive response'. Working with in vitro human lymphocytes, Wiencke (1987) has also demonstrated an enhancement of the X-ray induced adaptive response by nicotinamide. Similarly, in the present observations inter- and pretreatment of MMSchallenged mouse bone marrow cells with nicotinamide produced a significant reduction in chromosomal aberrations compared with the combined treatment at all recovery times (P < 0.05; Tables II–IV
). These data suggest that nicotinamide enhances the MMS-induced adaptive response in mouse bone marrow cells. In the post-treatment regimens there was a significant reduction in the frequency of chromosomal aberrations at 12 and 18 h, suggesting that nicotinamide protects the genetic system 6 h after the challenge treatment. This time lag in nicotinamide activity might be because the high dose of mutagen may have disturbed the genetic machinery, releasing the enzyme(s) required to repair the damage. The present results are consistent with earlier reports by the authors, which showed potentiation of the adaptive response to ethyl methanesulfonate by nicotinamide in vivo in the grasshopper P.pictus (Vasudev et al., 1999; Guruprasad et al., 2000) and in the mouse (Guruprasad and Vasudev, 2001).
The cytotoxicity of the chemicals was assessed as the mitotic index. The mitotic indices for the different treatment schedules show that nicotinamide did not affect the cell cycle (Table V) is in conformity with earlier reports (Snyder, 1984; Ben-Hur et al., 1985; Hunting et al., 1985).
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An indirect method of assessing PARP activity is NAD+ determination (Olsson et al., 1996
). NAD+ assay results have revealed that there is no significant variation in the amount of NAD+ in cells treated with the challenge dose or combined treatment compared with controls (P > 0.05; Figure 1) although there is a slight increase in the amount of NAD+ in the inter-treatment groups. Constancy of NAD+ levels signifies non-involvement of PARP activity. Further, in the presence of NAD+ the activity of Ca2+/Mg2+-dependent endonuclease, which fragments DNA, is inhibited (see Klaidman et al., 1996). In the present investigations the presence and constant level of NAD+ resulted in non-activity of Ca2+/Mg2+-dependent endonuclease and enhancement of the adaptive response. On a par with this, nicotinamide and other inhibitors of PARP are reported to prevent depletion of NAD+ in cells (de Murcia and Menisser de Murcia, 1994; Lindahl et al., 1995). Nicotinamide also acts as an anti-oxidant (Kamat and Devasagayam, 1999), anti-inflammatory (Pero et al., 1999), anti-diabetic (Kolb and Burkart, 1999) and anti-carcinogenic (Ludwig et al., 1990) agent. Further, there are reports of enhancement of DNA repair by inhibitors of PARP, including nicotinamide (Bohr and Klenow, 1981; Cleaver et al., 1985). Enhancement of the adaptive response by nicotinamide is another one of its multi-dimensional roles. Thus, both in vitro and in vivo, nicotinamide acts as a potentiator of the adaptive response (Wiencke, 1987; Vasudev et al., 1999; Guruprasad et al., 2000; Guruprasad and Vasudev, 2001).
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The above studies clearly indicate non-involvement of PARP in the MMS-induced adaptive response. Consistent with this, there are reports demonstrating DNA repair in cell extracts depleted of PARP (Rhun et al., 1998
) and PARP knockout mice (Wang et al., 1995). Furthermore, prokaryotes and some lower eukaryotes devoid of PARP carry out efficient DNA repair (Rhun et al., 1998) and the absence of PARP does not prevent DNA repair in vitro in keratinocytes (Ding et al., 1992). Nonetheless, dose-dependent synthesis of poly(ADP-ribose) polymers was observed in N-methyl-N-nitro-N-nitrosoguanidine-treated PARP–/– cells (Melissa et al., 1998). Caria et al. (1997) have also demonstrated an alternative repair pathway in the absence of PARP in in vitro human lymphocytes of Down syndrome patients. In conclusion, from our results and others it can be opined that nicotinamide acts as an enhancer of the adaptive response and that PARP is not involved in the MMS-induced adaptive response in vivo in mouse bone marrow cells.
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Acknowledgments |
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We wish to express our gratitude to the Professor and Chairman of the Department of Zoology for providing facilities and to the University Grants Commission for awarding the project contract no. F.3-58/93 (SR-II). K.P.G. is grateful to the CSIR, New Delhi, for financial assistance. The authors also thank Prof. M.Karunakumar (Biochemistry Department, University of Mysore), Mr Gangadhar (Zoology Department, University of Mysore) and Prof. Y.Srinivasa Reddy (Sericulture Department, University of Mysore) for their kind help during the course of this work. Thanks are also due to Dr Girish M.Shah (Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Canada) for suggesting the NAD+ assay to decipher the involvement of PARP in the adaptive response. We also thank an unknown referee for the pertinent comments by which it was possible for us to strengthen the results and improve the quality of the manuscript.
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5 To whom correspondence should be addressed
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References |
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-
Althaus,F.R. and Richter,C. (1987) ADP-ribosylation of proteins: enzymology and biological significance. Mol. Biol. Biochem. Biophys., 37, 1–237.[Medline]
Baranczewski,P., Nehls,P., Rieger,R., Rajewsky,M.F. and Schubert,I.S. (1997) Removal of O6-methyl guanine from plant DNA in vivo is accelerated under conditions of clastogenic adaptation. Environ. Mol. Mutagen., 29, 400–405.[Web of Science][Medline]
Ben-Hur,E., Chen,C.C. and Elkind,M.M. (1985) Inhibitors of poly(adenosine diphosphoribose) synthetase, examination of metabolic perturbations and enhancement of radiation response in Chinese hamster cells. Cancer Res., 45, 2123–2127.
Bohr,V. and Klenow,H. (1981) 3-Aminobenzamide stimulates unscheduled DNA synthesis and rejoining of strand breaks in human lymphocytes. Biochem. Biophys. Res. Commun., 102, 1254–1261.[Web of Science][Medline]
Caria,H., Quintas,A., Chaveca,T. and Rueff,J. (1997) The role of poly(ADP-ribose) polymerase in the induction of sister chromatid exchanges and micronucleus by mitomycin C in Down's syndrome cells as compared to euploid cells. Mutat. Res., 377, 269–277.[Web of Science][Medline]
Chatterjee,P.K., Cuzzocrea,S. and Thiemmermann,C. (1999) Inhibitors of PARS protects rat proximal tubular cells against oxidant stress. Kidney Int., 56, 973–984.[Web of Science][Medline]
Chatterjee,S. and Berger,N.A. (1994) Growth phase dependent response to DNA damage in poly(ADP-ribose) polymerase deficient cell lines: basis for a new hypothesis describing role of PARP in DNA replication repair. Mol. Cell. Biochem., 138, 61–69.[Web of Science][Medline]
Cleaver,J., Milam,K. and Morgan,W.F. (1985) Do inhibitors studies demonstrate a role for poly(ADP-ribose) in DNA repair. Radiat. Res., 101, 16–28.[Web of Science][Medline]
Cohen,J. and Duke,J. (1984) Glucocorticoid activation of a calcium dependent endonuclease in thymocyte nuclei leads to cell death. J. Immunol., 132, 38–42.[Abstract]
Cosi,C. and Marien,M. (1998) Decrease in mouse brain NAD+ and ATP induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): prevention by the poly(ADP-ribose) polymerase inhibitor, benzamide. Brain Res., 809, 58–67.[Web of Science][Medline]
Cosi,C., Suzuki,H., Milani,D., Facci,L., Menegazzi,M., Vatini,G., Kanai,Y. and Skaper,S.D. (1994) Poly(ADP-ribose) polymerase: early involvement in glutamate induced neurotoxicity in cultured cerebellar granule cells. J. Neurosci. Res., 39, 38–46.[Web of Science][Medline]
Cosi,C., Chopin,P. and Marien,M. (1996) Benzamide, an inhibitor of poly(ADP-ribose) polymerase, attenuates methamphetamine-induced dopamine neurotoxicity in the C57B1/6N mouse. Brain Res., 735, 343–348.[Web of Science][Medline]
de Murcia,G. and Menisser de Murcia,J. (1994) Poly(ADP-ribose) polymerase: a molecular nick sensor. Trends Biochem. Sci., 19, 172–176.[Web of Science][Medline]
Ding,R., Pommier,Y., Kang,V.H. and Smulson,M. (1992) Depletion of poly(ADP-ribose) polymerase by antisense RNA expression results in a DNA strand breaks rejoining. J. Biol. Chem., 267, 12804–12812.
Evans,E.P., Breckon,G. and Ford,C.E. (1964) Air drying method for meiotic preparations from mammalian testes. Cytogenetics, 3, 289–294.[Web of Science]
Guruprasad,K.P. and Vasudev,V. (2001) Inducible protective processes in animal systems: VIII. Enhancement of adaptive response by nicotinamide. Mutagenesis, 16, 257–263.
Guruprasad,K.P., Vasudev,V., Harish,S.K. and Venu,R. (2000) No role of poly(ADP-ribose) polymerase in EMS induced adaptive response in meiotic cells of Poecilocerus pictus. Proc. Radiat. Biol. DNA Damage Repair Carcinog., accepted for publication.
Harish,S.K., Guruprasad,K.P., Riaz Mahmood and Vasudev,V. (1998) Adaptive response to low dose of EMS or MMS in human peripheral blood lymphocytes. Indian J. Exp. Biol., 36, 1147–1150.[Medline]
Harish,S.K., Guruprasad,K.P., Riaz Mahmood and Vasudev,V. (2000) Inducible protective processes in animal systems: VI. Cross adaptation and the influence of caffeine on adaptive response in bone marrow cells of mouse. Mutagenesis, 15, 271–276.
Hunting,D.J., Gowans,B.J. and Henderson,J.F. (1985) Specificity of inhibitors of poly(ADP-ribose) synthesis. Effects on nucleotide metabolism in cultured cells. Mol. Pharmacol., 28, 200–206.[Abstract]
Ikushima,T., Aritomi,H. and Morisita,J. (1996) Radioadaptive response: efficient repair of radiation-induced DNA damage in adapted cells. Mutat. Res., 358, 193–198.[Web of Science][Medline]
Kaina,B. (1982) Enhanced survival and reduced mutation and aberration frequencies induced in V79 Chinese hamster cells pre-exposed to low levels of methylating agents. Mutat. Res., 93, 195–211.[Web of Science][Medline]
Kamat,J.P. and Devasagayam,T.P.A. (1999) Nicotinamide (vitamin B3) as an effective antioxidant against oxidative damage in rat brain mitochondria. Redox Rep., 4, 179–184.[Web of Science][Medline]
Klaidman,L.K., Mukerjee,S.K., Hutchin,T.P. and Adams,J.D. (1996) Nicotinamide as a precursor for NAD+ prevents apoptosis in the mouse brain induced by tertiary-butylhydroperoxide. Neurosci. Lett., 206, 5–8.[Web of Science][Medline]
Kleczkowska,H.E. and Althaus,F.R. (1996) Biochemical changes associated with the adaptive response of human keratinocytes to N-methyl-N-nitro-N-nitrosoguanidine. Mutat. Res., 368, 121–131.[Web of Science][Medline]
Klingenberg,M. (1975) Nicotinamide-adenine dinucleotides (NAD, NADP, NADH, NADPH) spectrophotometric and fluorimetric methods. Methods Enzymat. Anal., 4, 2045–2054.
Kolb,H. and Burkart,V. (1999) Nicotinamide in Type I diabetes. Mechanism of action revisited. Diabetes Care, 22, B16–B20.
Lankinen,M.H. and Vilpo,J.A. (1997) Repair of 
-irradiation induced single strand breaks in human bone marrow cells: effects of a second irradiation. Mutat. Res., 373, 31–37.[Web of Science][Medline]
Liazhen Zhang (1995) Cytogenetic adaptive response induced by pre-exposure in human lymphocytes and marrow cells of mice. Mutat. Res., 334, 33–37.[Web of Science][Medline]
Lindahl,T., Satoh,M.S., Poirior,G.G. and Klungland,A. (1995) Post translational modification of poly(ADP-ribose) polymerase induced by DNA strand breaks. Trends Biochem. Sci., 20, 405–411.[Web of Science][Medline]
Ludwig,A., Dietel,M., Schafer,G., Muller,K. and Hilz,H. (1990) Nicotinamide and nicotinamide analogues as antitumour promoters in mouse skin. Cancer Res., 30, 2470–2475.
Madhuri Jaju (1982) Cytogenetic effects of combined chemotherapy with anti-tubercular drugs on human lymphocytes. PhD thesis, Osmania University, Hyderabad, India.
Melissa,S.W., Ame,J.C., Wilson,M.V., Wang,Z.Q., Koh,D.W., Jacobson,M.K. and Jacobson,E.L. (1998) Poly(ADP-ribose) null mouse cells synthesize ADP-ribose polymers. J. Biol. Chem., 273, 30069–30072.
Mudrigal-Bujaidar,E., Cassani,M., Martinez,S. and Morales,T. (1994) Adaptive response induced by mitomycin C measuring the frequency of SCEs in human lymphocyte cultures. Mutat. Res., 322, 301–305.[Web of Science][Medline]
Nikolai,I.R., Antoshchina,M.M., Fesenko,E.V., Ivanova,T.I., Kondrashova,T.V. and Nasonova,V.A. (1998) Cytogenetic adaptive response in cultured human lymphocytes dependence on the time of exposure to adapting and challenging doses of -rays. Mutat. Res., 418, 7–19.[Web of Science][Medline]
Nikolova,T. and Huttner,E. (1996) Adaptive and synergistic effects of a low dose ENU pretreatment on the frequency of chromosomal aberrations induced by a challenge dose of ENU in human peripheral blood lymphocytes in vivo. Mutat. Res., 357, 131–141.[Web of Science][Medline]
Olivieri,G. and Bosi,A. (1990) Possible causes of the adaptive response in human lymphocytes. In Obe,G. and Natarajan,A.T. (eds), Chromosomal Aberrations: Basic and Applied Aspects. Springer-Verlag, Berlin, Germany, pp. 130–139.
Olivieri,G., Bodycote,J. and Wolff,S. (1984) Adaptive response of human lymphocytes to low concentration of radioactive thymidine. Science, 225, 10569–10571.
Olsson,A.R., Sheng,Y., Pero,R.W., Chaplin,D.J. and Horseman,M.R. (1996) DNA damage and repair in tumour and non-tumour tissues of mice induced by nicotinamide. Br. J. Cancer, 74, 368–373.[Web of Science][Medline]
Pero,R.W., Axelsson,B., Siemann,D., Chaplin,D. and Dougherty,G. (1999) Newly discovered anti-inflammatory properties of the benzamides and nicotinamides. Mol. Cell. Biochem., 193, 119–125.[Web of Science][Medline]
Rhun,Y.L., Kirkland,J.B. and Shah,G.M. (1998) Cellular response to DNA damages in the absence of poly(ADP-ribose) polymerase. Biochem. Biophys. Res. Commun., 245, 1–10.[Web of Science][Medline]
Riaz Mahmood and Vasudev,V. (1990) Inducible protective processes in animal systems: I. Clastogenic adaptation triggered by ethyl methanesulfonate (EMS) in Poecilocerus pictus. Biol. Zentralbl., 109, 41–43.
Riaz Mahmood and Vasudev,V. (1991) Inducible protective processes in animal systems: II. Absence of adaptive response when mitotic cells of mouse are exposed to low dose of EMS and challenged after short time lag. Cell Chromosom. Res., 14, 55–61.
Riaz Mahmood and Vasudev,V. (1992) Inducible protective processes in animal systems: III. Adaptive response of meiotic cells of grasshopper Poecilocerus pictus to low dose of ethyl methanesulfonate (EMS). Mutat. Res., 283, 243–247.[Web of Science][Medline]
Riaz Mahmood and Vasudev,V. (1993) Inducible protective processes in animal systems: IV. Adaptation of mouse bone marrow cells to low dose of ethyl methanesulfonate. Mutagenesis, 8, 83–86.
Riaz Mahmood, Vasudev,V., Harish,S.K. and Guruprasad,K.P. (1996) Inducible protective processes in animal systems: adaptive response to low dose of methyl methanesulfonate in mouse bone marrow cells. Indian J. Exp. Biol., 34, 502–507.[Medline]
Rieger,R., Michaelis,A. and Nicoloff,H. (1982) Inducible repair processes in plant root tip meristems? Below additivity effects' of unequally fractionated clastogen concentrations. Biol. Zentralbl., 101, 125–138.
Rieger,R., Michaelis,A. and Takahisa,S. (1990) An adaptive response of plant meristem cells in vivo protection against inducton of chromatid aberrations. In Obe,G. and Natarajan,A.T. (eds), Chromosomal Aberrations: Basic and Applied Aspects. Springer-Verlag, Berlin, Germany, pp. 163–179.
Samson,L. and Cairns,J. (1977) A new pathway for DNA repairing in E. coli. Nature, 267, 281–283.[Medline]
Samson,L. and Schwartz,J.L. (1980) Evidence for an adaptive DNA repair pathway in CHO and human skin fibroblast cell lines. Nature, 287, 861–863.[Medline]
Sankaranarayanan,K., Duyn,A.V., Loos,M.J. and Natarajan,A.T. (1989) Adaptive response of human lymphocytes to low level radiation from radioisotopes or X-rays. Mutat. Res., 211, 7–12.[Web of Science][Medline]
Shadley,J.D. and Wolff,S. (1987) Very low doses of X-rays can cause human lymphocytes to become less susceptible to ionizing radiation. Mutagenesis, 2, 95–96.
Snyder,R.D. (1984) 3-Aminobenzamide does not alter DNA repair in human fibroblasts through modulation of deoxynucleoside triphosphate pools. Biochem. Biophys. Res. Commun., 124, 457–461.[Web of Science][Medline]
Vasudev,V., Riaz Mahmood, Harish,S.K. and Guruprasad,K.P. (1997) Comparative analysis of error-free DNA repair (adaptive response) induced by EMS and MMS in Poecilocerus pictus and mouse. In Hemaprasad and Reddy,P.P. (eds), Environmental Pollution and Genetic Risk. Murthy Graphics, Hyderabad, India, pp. 59–68.
Vasudev,V., Guruprasad,K.P., Harish,S.K. and Venu,R. (1999) Inducible protective processes in animal systems: VII. Involvement of poly(ADP-ribose) polymerase (PARP) in EMS induced adaptive response in grasshopper Poecilocerus pictus meiotic cells. Proc. Acad. Environ. Biol., 8, 259–266.
Vogel,E. and Natarajan,A.T. (1982) The relation between reaction kinetics and mutagenic action of monofunctional alkylating agents in higher eukaryotic systems. In de Serres,F.J. and Hollaender,A. (eds), Chemical Mutagens: Principles and Methods for their Detection. Plenum Press, New York, NY, Vol. 7, pp. 295–336.
Wang,Z.Q., Auer,B., Stingle,L., Berghammer,H., Haidacher,D., Scheweiger,M. and Wagner,E.F. (1995) Mice lacking ADPRT and poly(ADP) ribosylation develop normally but are susceptible to skin diseases. Genes Dev., 9, 509–520.
Wiencke,J.K. (1987) Nicotinamide deficiency in human lymphocytes prevents [3H]thymidine-induced adaptive response for the repair of X-ray-induced chromosomal damage. Exp. Cell Res., 171, 518–523.[Web of Science][Medline]
Wiencke,J.K., Afzal,V., Olivieri,G. and Wolff,S. (1986) Evidence that [3H]thymidine-induced adaptive response of human lymphocytes to subsequent doses of X-rays involves the induction of a chromosomal repair mechanism. Mutat. Res., 1, 375–380.
Wolff,S. (1996) Aspects of the adaptive response to very low doses of radiation and other agents. Mutat. Res., 358, 135–142.[Web of Science][Medline]
Received on September 28, 2000; accepted on July 13, 2001.
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