Effect of cimetidine on in vivo formation of adducts between metabolites of benzo(a)pyrene and DNA.
Cimetidine has been reported to interact with liver microsomal enzymes, specifically, the cytochrome P-450 and P-448. Consequently cimetidine has the potential to impair the metabolism of compounds that undergo oxidative metabolism. The present study was designed to examine the benzo(a)pyrene-DNA adducts in the lungs and liver of mice after pretreatment with cimetidine. Male A/J mice received an i.p. dose of 40 mg/kg cimetidine followed by an oral dose of 5 micro mol/kg of [G-3H]BP 30 minutes apart. Control group received equal p.o. dose of BP. Animals (10 per group) were killed by cervical dislocation at 1h and 6h. The lungs and liver were removed and homogenized. DNA was then extracted, digested enzymatically to deoxyribonucleosides, and the adducts were analyzed by HPLC. The results showed that the percent of the adducts was reduced significantly.
Choong
M Y
MY
College of Pharmacy, Northeastern University, Boston, MA 02115.
Boroujerdi
M
M
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002927:Cimetidine / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice
D001564:Benzo(a)pyrene; D002927:Cimetidine; D004247:DNA