Evidence that DNA repair may not be modified by age or chronic caloric restriction.
Pretreatment of animals with mixed-function oxidase inducers has been shown to increase the metabolic activation capacity of isolated hepatocytes resulting in an apparent increase in DNA repair. We recently reported decreases in chemically-induced DNA repair, measured as unscheduled DNA synthesis (UDS), in hepatocyte cultures isolated from aging ad libitum (AL) and caloric restricted (CR) diet-fed animals. In the present study, we evaluated the effects of pretreatment with Aroclor 1254 (ARO) on the genotoxicity of 4 carcinogens, from different chemical classes, in primary hepatocytes isolated from male Fischer 344 rats. ARO-induced old AL- and CR-derived cultures, treated with 2-acetylaminofluorene (2-AAF), aflatoxin B1 (AFB1), 7,12-dimethylbenz[a]anthracene (DMBA), and dimethylnitrosamine (DMN), exhibited significant induction-related increases in DNA repair in comparison to uninduced old AL and CR animals. These data indicate that the constitutive levels of specific cytochrome P450 decline with age and chronic caloric restriction, while the ability to respond to exogenous inducers is retained, and suggest that DNA repair may not be modified with age or diet restriction.
Shaddock
J G
JG
Division of Genetic Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
Feuers
R J
RJ
Chou
M W
MW
Casciano
D A
DA
D015073:2-Acetylaminofluorene / Q000378:metabolism; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism; D016604:Aflatoxin B1 / Q000378:metabolism; D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001140:Aroclors / Q000633:toxicity; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair / Q000187:drug effects; D004032:Diet / Q000009:adverse effects; D004128:Dimethylnitrosamine / Q000378:metabolism; D002149:Energy Intake; D004790:Enzyme Induction; D005508:Food Deprivation; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D001140:Aroclors; D009153:Mutagens; D020111:Chlorodiphenyl (54% Chlorine); D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; D016604:Aflatoxin B1; D006899:Mixed Function Oxygenases; D004128:Dimethylnitrosamine