Dose-dependent benzo(a)pyrene [B(a)P]-DNA adduct levels and persistence in F-344 rats following subchronic dietary exposure to B(a)P.
In order to investigate the relationship between BaP-DNA adduct formation and long-term exposure to benzo(a)pyrene (BaP), DNA adduct levels in liver and lung tissues of male and female F-344 rats subchronically exposed to BaP were determined. Doses of 0, 5, 50, and 100mg/kg BaP, representing control, low, intermediate, and high doses, respectively, were administered in the animal diet over a 90-day period. After dosing, animals were sacrificed, liver and lung tissues were removed, DNA was isolated and analyzed for BaP-induced DNA adducts by the (32)P-postlabeling method using a four-directional thin-layer chromatography system. At low and intermediate BaP doses, DNA adduct levels in the tissues were significantly correlated with exposure. However, at high BaP doses, the dose-DNA adduct relationship became non-linear. Similarly, the relative DNA adducts persistence at intermediate and high doses were significantly higher than that measured at low dose. The low and intermediate dose linearity and high dose non-linearity may be due to saturation of metabolic activation and detoxification enzymes, and DNA repair processes.
Ramesh
Aramandla
A
Division of Cancer Biology, Department of Biomedical Sciences, Meharry Medical College, 1005 D.B. Todd Blvd, Nashville, TN 37208, USA. aramesh@mmc.edu
Knuckles
Maurice E
ME
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D018736:DNA Adducts / Q000378:metabolism*; D004032:Diet; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010761:Phosphorus Radioisotopes; D051381:Rats; D011916:Rats, Inbred F344
D002274:Carcinogens, Environmental; D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene