Effect of dietary restriction on benzo[a]pyrene (BaP) metabolic activation and pulmonary BaP-DNA adduct formation in mouse.
Hepatic microsomal xenobiotic metabolizing enzyme activities of laboratory animals can be modulated by Dietary restriction (DR). The modulation of xenobiotic metabolizing enzyme activities can affect the metabolic activation of chemical carcinogens. Acute DR (60% of the food consumption of ad libitum (AL)-fed mice for 7 weeks) reduced the body weights of the male B6C3F1 mice, and increased mouse pulmonary cytochrome P4501A1-dependent BaP metabolizing enzyme activity. The effects of DR on the formation of the specific BaP-DNA adduct, 10-(N2-deoxyguanosinyl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-BaP (BaP-N2-dG) in mouse lung can be detected by using 32P-postlabeling technique. In both AL- and DR-mice total BaP-DNA adduct formation in lung reached a peak at 48 hours after treatment with [3H]BaP and the in vivo formation of BaP-N2-dG was greater in DR mouse lung than in that of AL-animals by 22%. DR increased in vitro BaP-N2-dG formation by 39% when calf-thymus DNA was incubated with BaP using liver microsomes obtained from DR- or AL-mice as the enzyme source. The formation of the specific BaP-N2-dG adducts, measured by 32P-postlabeling, was only 20% of the total [3H]BaP-DNA adducts as determined by liquid scintillation counting. The increase of BaP-DNA adduct formation in mouse lung was correlated to the enhancement of the mouse pulmonary BaP metabolizing enzyme activity. Our results indicated that the effect of DR on the metabolic activation of BaP in mouse lung was dependent upon the mouse lung cytochrome P4501A1-dependent BaP metabolizing enzymes activities which was significantly increased by DR.
Chen
W
W
National Center for Toxicological Research, Jefferson, AR, USA.
Zhou
Y
Y
Nichols
J
J
Chung
K T
KT
Hart
R W
RW
Chou
M W
MW
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000493:pharmacokinetics*; D001579:Benzopyrene Hydroxylase / Q000378:metabolism / Q000494:pharmacology; D001711:Biotransformation; D001835:Body Weight / Q000502:physiology; D002273:Carcinogens / Q000378:metabolism / Q000493:pharmacokinetics*; D002855:Chromatography, Thin Layer; D018736:DNA Adducts / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005508:Food Deprivation / Q000502:physiology*; D008168:Lung / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008861:Microsomes / Q000502:physiology; D009929:Organ Size; D010761:Phosphorus Radioisotopes; D013997:Time Factors; D015430:Weight Gain
D002273:Carcinogens; D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D001564:Benzo(a)pyrene; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases