Activity of some nuclear enzymes associated with DNA repair following hepatocarcinogen administration to rats.
Administration of hepatocarcinogens aflataxin B1 (AFB1) and N-nitrosodimethylamine (NDMA) to rats caused single-strand breaks in hepatic nuclear DNA. The damage was found to be maximum at 4 hours following AFB1 administration and at 2 hours following NDMA administration. These damages were repaired after 17 and 4 hours, respectively in cases of AFB1 and NDMA. The activity of poly(ADP-ribose)polymerase (PARP), an enzyme known to use single-strand breaks of DNA as cofactor, was observed to increase with increasing damage to DNA and decrease as and when this damage got repaired. DNA polymerase beta and DNA ligase activities were also seen to increase and decline in a way analogous to PARP. In contrast, DNA topoisomerase activity declined corresponding to an increase in PARP activity. These observations suggest a possible role of PARP in coordinating the activities of other enzymes involved in DNA repair. It is also envisaged that these parameters can be utilized to devise strategies to counteract the deleterious effects of chemical carcinogens.
Webster
R P
RP
Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Bombay, India.
Bhattacharya
R K
RK
D016604:Aflatoxin B1 / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002467:Cell Nucleus / Q000201:enzymology; D002499:Centrifugation, Density Gradient; D004249:DNA Damage; D011088:DNA Ligases / Q000378:metabolism*; D004256:DNA Polymerase I / Q000378:metabolism*; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D002273:Carcinogens; D016604:Aflatoxin B1; D011065:Poly(ADP-ribose) Polymerases; D004256:DNA Polymerase I; D004264:DNA Topoisomerases, Type I; D011088:DNA Ligases; D004128:Dimethylnitrosamine