Metabolism of benzo[a]pyrene-7,8-dihydrodiol and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide to protein-binding products and glutathione conjugates in isolated rat hepatocytes

Isolated hepatocytes from 3-methylcholanthrene (MC)-treated rats metabolized trans-7, 8-dihydroxy-7, 8-dihydrobenzo[a]pyrene (BP-7, 8-diol) and (± )-7β, 8α-dihydroxy-9α, 10α-oxy-7, 8, 9, 10-tetrahydrobenzo[a]pyrene (anti-BPDE) to water soluble conjugates including glutathione (GSH) conjugates. Under...

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Bibliographic Details
Published in:Carcinogenesis (New York) 1984-08, Vol.5 (8), p.1079-1085
Main Authors: Jernström, Bengt, Martinez, Margareta, Svensson, Sten-Åke, Dock, Lennart
Format: Article
Language:English
Subjects:
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
Animals
Benzoflavones - pharmacology
Benzopyrenes - metabolism
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Chemical agents
Chromatography, High Pressure Liquid
Dihydroxydihydrobenzopyrenes
Glutathione - metabolism
Liver - drug effects
Liver - metabolism
Macromolecular Substances
Male
Maleates - pharmacology
Medical sciences
Proteins - metabolism
Rats
Rats, Inbred Strains
Spectrometry, Fluorescence
Tumors
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Summary:Isolated hepatocytes from 3-methylcholanthrene (MC)-treated rats metabolized trans-7, 8-dihydroxy-7, 8-dihydrobenzo[a]pyrene (BP-7, 8-diol) and (± )-7β, 8α-dihydroxy-9α, 10α-oxy-7, 8, 9, 10-tetrahydrobenzo[a]pyrene (anti-BPDE) to water soluble conjugates including glutathione (GSH) conjugates. Under the conditions employed 35% of total water soluble products derived from BP-7, 8-diol could be accounted for by GSH conjugates. The corresponding figure for anti-BPDE was estimated to be >80%. Isolated hepatocytes metabolized BP-7, 8-diol and anti-BPDE to GSH conjugates at maximal rates of 0.5 and 9 nmol per 106 cells per min, respectively. Thus, identifying the rate limiting step in the reaction sequence as the metabolism of BP-7, 8-diol to the GSH conjugating intermediates. In addition to the direct conjugation of anti-BPDE with GSH, anti-BPDE but not the corresponding BP-tetraols, was further metabolized to reactive intermediates that subsequently bound to cellular proteins or reacted with GSH forming water soluble conjugates. The identity or identities of these novel reactive intermediates is discussed.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/5.8.1079