Biomaterial Database

Benzo[a]pyrene metabolism and DNA adduct formation mediated by English sole liver enzymes. 1985

M Nishimoto, and U Varanasi

Tritiated benzo[a]pyrene (BaP) and (+/-)-7,8-dihydroBaP (BaP 7,8-dihydrodiol) were incubated with English sole liver microsomes in the presence of salmon testes DNA. The modified deoxynucleosides were isolated by Sephadex LH-20 column chromatography and analyzed by reverse-phase high-pressure liquid chromatography (HPLC). A single, major adduct (60-68% of the total modified deoxynucleosides) was formed when either BaP or BaP 7,8-dihydrodiol was incubated with sole liver microsomes and DNA. Although other minor BaP-DNA adducts were formed, none represented greater than 3% of the total adducts. The major adduct had a retention time on HPLC identical to that of the N2-[10 beta (7 beta, 8 alpha, 9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene)yl]-deoxy-guanosine (7R-anti-BPDE/trans-dG) adduct formed when anti-BPDE, the ultimate carcinogen of BaP in mammals, was incubated with DNA. Analysis of the Bay region tetrols showed that only the 7 alpha, 8 beta, 9 beta, 10 alpha-tetrahydroxy-7,8,9,10-tetrahydroBaP, a hydrolysis product of the anti-BPDE, was formed when BaP was incubated with sole liver microsomes. When BaP 7,8-dihydrodiol was used as the substrate, the 7 alpha, 8 beta, 9 beta, 10 alpha-, 7 alpha, 8 beta, 9 alpha, 10 beta-, and 7 alpha, 8 beta, 9 alpha, 10 alpha-tetrahydroxy-7,8,9,10-tetrahydroBaP's were formed, indicating the formation of both anti- and syn-BPDE. The ratio of tetrols of anti-BPDE/syn-BPDE was 2; however, the ratio of adducts of anti-BPDE/syn-BPDE was 20. Thus, the findings show that hepatic microsomes of English sole, a fish species having a high incidence of liver neoplasia in chemically contaminated estuaries, metabolized BaP and BaP 7,8-dihydrodiol stereoselectively to form predominantly the 7R-anti-BPDE/trans-dG adduct.

UI	MeSH Term	Description	Entries
D008862	Microsomes, Liver	Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.	Liver Microsomes,Liver Microsome,Microsome, Liver
D004101	Dihydroxydihydrobenzopyrenes	Benzopyrenes saturated in any two adjacent positions and substituted with two hydroxyl groups in any position. The majority of these compounds have carcinogenic or mutagenic activity.	Benzopyrene Dihydrodiols,Dihydrobenzopyrene Diols,Dihydrodiolbenzopyrenes,Dihydrodiols, Benzopyrene,Diols, Dihydrobenzopyrene
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
D005399	Fishes	A group of cold-blooded, aquatic vertebrates having gills, fins, a cartilaginous or bony endoskeleton, and elongated bodies covered with scales.
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
D001580	Benzopyrenes	A class of chemicals that contain an anthracene ring with a naphthalene ring attached to it.	Benzpyrene
D066298	In Vitro Techniques	Methods to study reactions or processes taking place in an artificial environment outside the living organism.	In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In