Glucuronide conjugation reduces the cytotoxicity but not the mutagenicity of benzo(a)pyrene in the CHO/HGPRT assay

Journal Article · Sun Jan 01 04:00:00 EST 1984 · Teratog., Carcinog., Mutagen.; (United States)

DOI:https://doi.org/10.1002/tcm.1770040503· OSTI ID:5877459

Recio, L; Hsie, A W

Benzo(a)pyrene (B(a)P) is biotransformed by the mixed-function oxidase (MFO) system to numerous metabolites some of which are cytotoxic and/or mutagenic to mammalian cells. However, conjugation of B(a)P-induced metabolites with glucuronic acid in vivo is a major pathway of detoxication and elimination. The effects of glucuronide conjugation on B(a)P-induced cytotoxicity and mutagenicity were studied using the CHO-HGPRT assay with a rat liver homogenate preparation containing MFO system cofactors (S9 mix) and uridine diphosphate ..cap alpha..-D-glucuronic acid (UDPGA). B(a)P metabolites proximate to the biologically active B(a)P quinones (B(a)P 6-OH) and to the B(a)P 7,8-diol-9,10 epoxide isomers (B(a)P 7,8-diol), were also assayed with S9 mix in the absence and presence of UDPGA. The addition of UDPGA to S9 mix reduced B(a)P-induced cytotoxicity but did not affect mutagenicity. B(a)P 6-OH-mediated cytotoxicity was also reduced in the presence of UDPGA. UDPGA had no effect on B(a)P 7,8-diol-induced cytotoxicity or mutagenicity. B(a)P phenols have been shown to be the preferred B(a)P metabolite substrates for UDP-glucuronyltransferase enzymes. Thus, the reduction of B(a)P and B(a)P 6-OH-induced cytotoxicity by glucuronide conjugation is likely due to the elimination of cytotoxic phenols and quinones. Since B(a)P 7,8-diol is a poor substrate for UDP-glucuronyltransferase enzymes, no effects on B(a)P-induced mutagenicity or B(a)P 7,8-diol-induced cytotoxicity and mutagenicity were observed. 40 references, 3 figures, 2 tables.

• Research Organization: Univ. of Kentucky, Lexington
• DOE Contract Number: AC05-84OR21400
• OSTI ID: 5877459
• Journal Information: Teratog., Carcinog., Mutagen.; (United States), Journal Name: Teratog., Carcinog., Mutagen.; (United States) Vol. 4; ISSN TCMUD
• 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.
ALDEHYDES
ANIMAL CELLS
ANIMALS
AROMATICS
BENZOPYRENE
BIOLOGICAL EFFECTS
BODY
CARBOXYLIC ACIDS
CHO CELLS
CONDENSED AROMATICS
DATA
DETOXIFICATION
DIGESTIVE SYSTEM
DOSE-RESPONSE RELATIONSHIPS
EXPERIMENTAL DATA
GLANDS
GLUCURONIC ACID
HYDROCARBONS
HYDROXY ACIDS
INFORMATION
LIVER
MAMMALS
METABOLIC ACTIVATION
METABOLITES
MUTAGEN SCREENING
MUTAGENESIS
NUMERICAL DATA
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RATS
RODENTS
SCREENING
TOXICITY
VERTEBRATES