The influence of fluoranthene on the metabolism and DNA binding of benzo[a]pyrene in vivo in mouse skin.
The effect of the cocarcinogen fluoranthene on the DNA binding and metabolism of [3H]benzo[a]pyrene (B[a]P) in vivo in mouse skin has been investigated. In the presence of fluoranthene the level of B[a]]P-DNA binding was increased at each of the time intervals examined (4, 8, 24 and 48 h) with enhancements ranging from 76% at 4 h to 36% at 48 h. The ratio of anti-7,8,-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE)-DNA adducts/syn-BPDE-DNA adducts was also increased in the presence of fluoranthene. This increase was greatest at 8 h (44%) but by 48 h the ratio was identical in the presence and absence of fluoranthene. The observed increase in anti-BPDE-DNA adducts/syn-BPDE-DNA adducts did not parallel increases in B[a]P-DNA binding suggesting that alteration of the anti-BPDE/syn-BPDE ratio is not a major contributing factor to the cocarcinogenic activity of fluoranthene. The influence of fluoranthene on the metabolism of B[a]P in vivo in mouse skin was also investigated. Fluoranthene was found to have little or no effect on the formation of ethyl acetate extractable metabolites of B[a]P in mouse skin. Specifically, there was no increase in the amount of B[a]P-7,8-diol in the presence of fluoranthene. Fluoranthene also had little or no effect on the levels of beta-glucuronide or sulfate conjugates of B[a]P metabolites formed in vivo in mouse skin. These studies suggest that the effect of fluoranthene is being expressed at some point after B[a]P has been activated to an ultimate carcinogen.
Rice
J E
JE
Rutgers University, College of Pharmacy, Department of Pharmaceutical Chemistry, Piscataway, NJ 08854.
Defloria
M C
MC
Sensenhauser
C
C
Lavoie
E J
EJ
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects; D002274:Carcinogens, Environmental / Q000633:toxicity*; D003043:Cocarcinogenesis; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D018736:DNA Adducts; D004305:Dose-Response Relationship, Drug; D005260:Female; D005449:Fluorenes / Q000633:toxicity*; D051379:Mice; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
D002274:Carcinogens, Environmental; D018736:DNA Adducts; D005449:Fluorenes; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; C007738:fluoranthene; D004247:DNA