The influence of fluoranthene on the metabolism and DNA binding of benzo[a]pyrene in vivo in mouse skin. 1988

J E Rice, and M C Defloria, and C Sensenhauser, and E J Lavoie
Rutgers University, College of Pharmacy, Department of Pharmaceutical Chemistry, Piscataway, NJ 08854.

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.

UI MeSH Term Description Entries
D002274 Carcinogens, Environmental Carcinogenic substances that are found in the environment. Environmental Carcinogens
D003043 Cocarcinogenesis The combination of two or more different factors in the production of cancer. Cocarcinogeneses
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D005449 Fluorenes A family of diphenylenemethane derivatives.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001564 Benzo(a)pyrene A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. 3,4-Benzopyrene,3,4-Benzpyrene,3,4 Benzopyrene,3,4 Benzpyrene
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012867 Skin The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.

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