Mutation induction at multiple gene loci in Chinese hamster ovary cells: comparisons of benzo(a)pyrene metabolism by organ homogenates and intact cells
Mutations induced by B(a)P are quantified at four gene loci in Chinese hamster ovary (CHO) cells: aprt, hgprt, tk, and ATPase. The mutants were selected by their resistance to 8-azaadenine (AA), 6-thioguanine (TG), 5-fluorodeoxyuridine (FUdR), or ouabain (OUUA). Activation by liver homogenates (S9) and liver microsomes from rats induced with Aroclor 1254, Syrian hamster embryo (SHE) cells, and kidney microsomes from male, female, and testosterone-treated female C3H/HeJ mice was compared. Finally, a comparison was made between profiles of B(a)P metabolites produced by the different activation systems and th observed mammalian mutagenesis data. Comparison of profiles of B(a)P metabolites produced by different activation systems with the observed mutagenic activity at four gene loci in a mammalian mutagenesis system showed some striking similarities but some significant differences. Although profiles of SHE-activated B(a)P represent metabolism that is more relevant to the intact cell than to disrupted cell homogenates, induced mutation levels at four separate gene loci were very similar for B(a)P activated by rate liver microsomes or SHE. Thus dissimilar activation systems may produce similar steady-state levels of the mutagenic epoxide intermediates. However, the frequencies of B(a)P mutation with S9 activation were substantially lower. Kidney microsomes from male and testosterone-treated female mice efficiently metabolized DMN, but produced insignificant amounts of B(a)P metabolites; mutation data paralleled these results. (ERB)
- Research Organization:
- California Univ., Livermore (USA). Lawrence Livermore Lab.
- DOE Contract Number:
- W-7405-ENG-48
- OSTI ID:
- 5637373
- Report Number(s):
- UCRL-82566; CONF-791059-2
- Resource Relation:
- Conference: 4. international symposium on polynuclear aromatic hydrocarbons, Columbus, OH, USA, 2 Oct 1979
- Country of Publication:
- United States
- Language:
- English
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Comparison of benzo(a)pyrene metabolism and mutation induction in CHO cells using rat liver homogenate (S9) or Syrian hamster embryonic cell-mediated activation systems
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Related Subjects
ANIMAL CELLS
GENE MUTATIONS
BENZOPYRENE
METABOLISM
MUTAGENESIS
METABOLITES
MUTAGEN SCREENING
CELL CULTURES
COMPARATIVE EVALUATIONS
EXPERIMENTAL DATA
HOMOGENATES
ISOLATED VALUES
TISSUE EXTRACTS
AROMATICS
BIOLOGICAL MATERIALS
BODY
CONDENSED AROMATICS
DATA
DATA FORMS
HYDROCARBONS
INFORMATION
MATERIALS
MUTATIONS
NUMERICAL DATA
ORGANIC COMPOUNDS
SCREENING
TISSUES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)