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Title: The metabolism of benzo(a)pyrene by respiratory tissues
Author: Moore, Brian P.
ISNI:       0000 0001 3415 7151
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1979
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Benzo(a)pyrene was metabolised by short-term organ cultures of human, rat or hamster lung and hamster or rat trachea to ethyl acetate-soluble and water-soluble metabolites. 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene (7,8-dihydrodiol), 9,10-dihydro-9,10-dihydroxybenzo(a)pyrene (9,10-dihydrodiol) and benzo(a)pyren-3-yl-hydrogen sulphate were identified as the prevalent ethyl acetate-soluble metabolites with little or no monohydroxybenzo(a)pyrenes or 4,5-dihydro-4,5-dihydroxybenzo(a)pyrene (4,5-dihydrodiol). A large proportion of the water-soluble metabolites from shortterm cultures of lung or trachea from rats or hamsters consisted of glucuronide conjugates, the main ones being those of 3-hydroxybenzo (a)pyrene, 4,5-dihydrodiol and 1(3),9,10-trihydroxy-9,10-dihydrobenzo (a)pyrene. Similar ethyl acetate-soluble metabolites were detected following isolated rat lung perfusion with benzo(a)pyrene excepting that rather more monohydroxybenzo(a)pyrenes and quinones were produced. These results were extended by studying the further metabolism of 3-hydroxybenzo(a)pyrene, 4,5-dihydrodiol, 7,8-dihydrodiol and 9,10-dihydrodiol. The principle ethyl acetate-soluble products following cultures with dihydrodiols were further hydroxylated metabolites whereas the main product from 3-hydroxybenzo(a)pyrene was benzo(a)pyren-3-yl-sulphate. Both 7,8-dihydrodiol and 9,10-dihydrodiol (to a lesser extent) were metabolised to a material which was identified as 7,8,9,10-tetrahydro-7,8,9,10-tetrahydroxybenzo (a) pyrene. The main water-soluble metabolites from each of the four starting materials were identified as glucuronide conjugates and in all but the case of 9,10-dihydrodiol it appeared that the product was formed directly by conjugation of a hydroxyl group with uridine-diphosphate glucuronic acid. The major glucuronide conjugate from 9,10-dihydrodiol was identified as that of 1(3),9,10-trihydroxy-9,10-dihydrobenzo(a) pyrene with little or no material conjugated directly. Benzo(a)pyrene, 3-hydroxybenzo(a)pyrene, 4,5-dihydrodiol, 7,8-dihydrodiol, 9,10-dihydrodiol and 1(3),9,10-trihydroxy-9,10-dihydro benzo(a)pyrene bound with ligandin, aminoazodye binding protein A and liposomes. 9,10-Dihydrodiol and 1(3),9,10-trihydroxy-9,10-dihydroxybenzo(a)pyrene bound significantly less than other metabolites to aminoazodye binding protein A and liposomes. DNA-benzo(a)pyrene adducts were investigated following isolated rat lung perfusion with benzo(a)pyrene. A single type of adduct was found and identified as that produced by the interaction of 7a, 83-dihydroxy-93, 103-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (anti diol-epoxide) with the 2 amino group of guanine. The formation of this adduct was increased approximately 10-fold by pretreatment of animals with 3-methylcholanthrene.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available