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Metabolism of benzo[a]pyrene by cultured tracheobronchial tissues from mice, rats, hamsters, bovines and humans
Author(s) -
Autrup Herman,
Wefald Franklin C.,
Jeffrey Alan M.,
Tate Hussein,
Schwartz Rochelle D.,
Trump Benjamin F.,
Harris Curtis C.
Publication year - 1980
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910250219
Subject(s) - carcinogen , hamster , metabolite , pyrene , benzo(a)pyrene , chinese hamster , metabolism , biochemistry , chemistry , benzopyrene , dna , glutathione , mesocricetus , biology , microbiology and biotechnology , organic chemistry , enzyme
The metabolism of benzo[a]pyrene (BP) 4 by cultured tracheobronchial tissues from different species ‐ human, bovine, hamster, rat and mouse ‐ has been investigated. The total metabolism, as measured by both organic solvent‐extractable and water‐soluble metabolites of BP, was substantial in the respiratory tract from humans and from animal species susceptible to the carcinogenic action of BP. The ratio of organic‐extractable metabolites to water‐soluble metabolites was greater than one in hamster, human and C57BI/6N mouse, but less than one in rat, bovine and DBA/2N mouse, suggesting that determination of both activation and deactivation pathways are important in assessing carcinogenic risk of a chemical. Sulphate esters and glutathione conjugates were the major water‐soluble metabolites in all animal species; tetrols and diols were the major organic extractable metabolites. The level of trans‐7,8‐dihydro‐7,8‐dihydroxybenzo[a]pyrene, the proximate carcinogenic form of BP, was three times higher in C57BI/6N than in DBA/2N mouse trachea. Trans‐9,10‐dihydro‐9,10‐dihydroxybenzo[a]pyrene was the major metabolite formed by cultured hamster trachea. The binding levels of BP to cellular DNA were quite similar in all tissues, although slightly higher binding was observed in hamster trachea. Wide inter‐individual variation in the binding of BP to DNA was seen in tissues from outbred species. The major BP‐DNA adducts in all animal species were formed by interaction of benzo[a]pyrene diol‐epoxide with the 2‐amino group of deoxyguanosine. Both stereoisomeric forms of (±)‐(7β,8α)‐dihydroxy‐(9α, 10α)‐epoxy‐7,8,9,10‐tetrahydro‐benzo[a]pyrene (BPDE I) reacted with deoxyguanosine, the (7R)‐form being the most reactive. No difference in the relative distribution of the various adducts was seen between the species except in the CD rat, where BPDE‐deoxyadenosine adducts accounted for 20% of the total modification. In cultured hamster trachea the persistence of the different adducts was similar. In conclusion, the metabolism of BP is qualitatively similar in tracheobronchial tissues from both humans and animal species in which BP has been experimentally shown to be carcinogenic.