Detoxication mechanisms of benzo(a)pyrene as studied in the CHO/HGPRT assay

Conference · Mon Dec 31 23:00:00 EST 1984

OSTI ID:6376461

Recio, L; Hsie, A W

We have investigated the biological effects of glucuronide and glutathione conjugation on BaP-induced cytotoxicity and mutagenicity. Our studies demonstrate that glucuronide conjugation of BaP results in a reduction of cytotoxicity without affecting mutagenicity. This is likely due to an elimination of cytotoxic phenols and quinones without affecting the formation and bioactivation of BaP 7,8-diol to the ultimate mutagenic form of BaP. GSH conjugation of BaP catalyzed by GSHTs inhibits the cytotoxicity and mutagenicity of BaP 7,8-diol in a concentration-dependent manner. These are consistent with and supported by biochemical studies on the biotransformation of BaP and DNA binding by bioactivated BaP. We conclude that these two enzyme systems have overlapping and complimentary roles in the detoxication of BaP. The activity of these enzyme systems in vivo can profoundly affect the biological activity of BaP and other PAH. 13 refs., 3 figs., 2 tabs.

• Research Organization: Kentucky Univ., Lexington (USA). Graduate Center for Toxicology; Oak Ridge National Lab., TN (USA)
• DOE Contract Number: AC05-84OR21400
• OSTI ID: 6376461
• Report Number(s): CONF-851068-4; ON: DE86004778
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ANIMAL CELLS
AROMATICS
BENZOPYRENE
CHO CELLS
CONDENSED AROMATICS
DATA
ENZYMES
EXPERIMENTAL DATA
GENE MUTATIONS
GLUCURONIDE CONJUGATES
GLUTATHIONE CONJUGATES
GLYCOLS
GLYCOSYL TRANSFERASES
HYDROCARBONS
HYDROXY COMPOUNDS
HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE
INFORMATION
METABOLISM
METABOLITES
MUTAGENESIS
MUTATIONS
NUMERICAL DATA
ORGANIC COMPOUNDS
PENTOSYL TRANSFERASES
TRANSFERASES