The effects of dietary restriction and aging on in vivo and in vitro binding of aflatoxin B1 to cellular DNA.
Laboratory animals maintained on a reduced calorie but nutritionally adequate diet have extended life spans and lowered incidences of spontaneous and chemically induced cancers compared to ad libitum- fed counterparts. Many of the effects of dietary restriction on laboratory animals have been suggested to be related to a deceleration of the aging process. The inhibition of age-related changes in xenobiotic metabolizing enzymes activities by dietary restriction has previously been reported. Alterations of these enzyme activities may cause changes in metabolic activation of carcinogens and, therefore, carcinogen-DNA binding. DNA-repair capability has also been reported to be enhanced in diet-restricted rats. Using AFB1 as a model carcinogen, we have studied in vivo and in vitro hepatic AFB1-DNA binding, demonstrating that dietary restriction (60% of ad libitum consumption) may decrease the metabolic activation of AFB1, and subsequently reduce AFB1-DNA binding. Our preliminary results obtained from the AFB1-DNA binding experiments in isolated hepatocytes suggest that the observed age-dependent reduction in AFB1-DNA binding which may be attributed to a loss of metabolic activating capability was delayed in the diet-restricted rats.
Chou
M W
MW
National Center for Toxicological Research, Jefferson, Arkansas, AR 72079.
Pegram
R A
RA
Gao
P
P
Hansard
S R
SR
Shaddock
J G
JG
Casciano
D A
DA
D016604:Aflatoxin B1 / Q000378:metabolism* / Q000493:pharmacokinetics; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D004247:DNA / Q000378:metabolism*; D004032:Diet; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D015262:Xenobiotics / Q000378:metabolism
D015262:Xenobiotics; D004247:DNA; D016604:Aflatoxin B1