Individual differences in DNA repair capacities in man.
After metabolic activation of benzo[a]pyrene to the 7,8-dihydrodiol-9,10-epoxide, this ultimate carcinogen preferentially binds to the exocyclic amino group of guanine. In order to investigate possible interindividual differences in the capacity of repair of the DNA adducts formed from benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide, their persistence in freshly isolated lymphocytes of several donors was studied. The results show a surprisingly large interindividual variation in DNA adduct formation and their persistence in freshly isolated lymphocytes. This range included several individuals with an apparent complete lack of repair capability for these adducts. Compared with controls, smokers showed on average a lower initial extent of the DNA adducts formed from benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide, suggesting induction of inactivating enzymes. However, one of the smokers was an individual with apparent complete lack of repair for the DNA adducts formed from benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide, combining exposure to benzo[a]pyrene with a long persistence of the DNA adducts formed from benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide. The investigation of the DNA repair of methylnitrosourea-induced lesions showed significant interindividual differences in the adaptive response triggered by repeated exposure to the carcinogen, whereas the interindividual variations after single doses were low.
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000097:blood*; D000478:Alkylation; D002478:Cells, Cultured; D004247:DNA / Q000097:blood*; D018736:DNA Adducts; D004260:DNA Repair; D004101:Dihydroxydihydrobenzopyrenes / Q000097:blood*; D006147:Guanine / Q000031:analogs & derivatives / Q000097:blood; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism*
D018736:DNA Adducts; D004101:Dihydroxydihydrobenzopyrenes; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D006147:Guanine; D004247:DNA; C008449:O-(6)-methylguanine