Modulation of benzo(a)pyrene-induced toxicity and mutagenicity by conjugation enzymes in mammalian cells (CHO/HGPRT Assay)
The biotransformation of benzo(a)pyrene (BP) catalyzed by the mixed-function oxidase (MFO) system results in numerous metabolites which are cytotoxic and/or mutagenic to mammalian cells. However, these are conjugated with endogenous compounds such as glucuronic acid, sulfate and glutathione (GSH) resulting in detoxication. The effects of three conjugation enzyme systems, UDP-glucuronyltransferases (UDP-GT), sulfotransferases (ST) and glutathione S-transferases (GSHT) on BP-induced cytotoxicity and mutagenicity were studied using the Chinese hamster ovary cells/hypoxanthine-guanine phosphoribosyltransferase (CHO/HGPRT) assay. These studies were done by supplementing a rat-liver homogenate preparation containing MFO system cofactors. The relationship between BP 7,8-diol-9,10-epoxide (BPDE)-DNA adducts and mutagenicity in the CHO/HGPRT assay was also determined. The results of these studies are discussed. 149 refs., 11 figs., 11 tabs.
- Research Organization:
- Kentucky Univ., Lexington (USA)
- DOE Contract Number:
- AC05-76OR00033; AC05-84OR21400
- OSTI ID:
- 6768312
- Report Number(s):
- DOE/OR/00033-T411; ON: DE88015644
- Resource Relation:
- Other Information: Thesis (Ph.D.). Portions of this document are illegible in microfiche products
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BENZOPYRENE
DAUGHTER PRODUCTS
MUTAGENS
DETOXIFICATION
TOXICITY
BIOASSAY
CLASSIFICATION
HAMSTERS
RATS
SEPARATION PROCESSES
ANIMALS
AROMATICS
CONDENSED AROMATICS
HYDROCARBONS
ISOTOPES
MAMMALS
ORGANIC COMPOUNDS
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology