Quantitative mammalian cell genetic toxicology: study of the cytotoxicity and mutagenicity of 70 individual environmental agents related to energy technologies and 3 subfractions of a crude synthetic oil in the CHO/HGPRT system. [Hamsters]

Technical Report · Sun Jan 01 04:00:00 EST 1978

DOI:https://doi.org/10.2172/5114391· OSTI ID:5114391

Hsie, A W; Neill, J P; San Sebastian, J R

Conditions necessary for quantifying mutation-induction to 6-thioguanine resistance, which selects for >98% mutants deficient in the activity of hypoxanthine-guanine phosphoribosyl transferase (HGPRT) in a near-diploid Chinese hamster ovary (CHO) cell line, referred to as CHO/HGPRT system, have been defined. Employing this mutation assay, we have determined the mutagenicity of diversified agents including 11 direct-acting alkylating agents, 16 nitrosamines, 10 heterocyclic nitrogen mustards, 15 metallic compounds, 5 quinolines, 5 aromatic amines, 27 polycyclic hydrocarbons, 13 miscellaneous chemicals, 7 ionizing and non-ionizing physical agents. The direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine is mutagenic while its noncarcinogenic analogue N-methyl-N'-nitro-N-nitroguanidine is not. Coupled with the rat liver S/sub 9/-activation system, procarcinogens such as nitrosopyrrolidine, benzo(a)pyrene, and 2-acetylaminofluorene are mutagenic while their analogues 2,5-dimethylnitrosopyrrolidine, pyrene and fluorene are not. The assay appears to be applicable for monitoring the genetic toxicity of crude organic mixtures in addition to diverse individual chemical and physical agents. The quantitative nature of the assay enables a study of EMS exposure dose: the mutagenic potential of EMS can be described as 310 x 10/sup -6/ mutants (cell mg ml/sup -1/ h)./sup -1/ It is also feasible to expand the CHO/HGPRT system for quantifying cytotoxicity and mutagenicity to determination of chromosomal aberrations and sister chromatid exchanges in cells treated under identical conditions which allows a simultaneous study of these four distinctive biological effects.

• Research Organization: Oak Ridge National Lab., Tenn. (USA); Tennessee Univ., Oak Ridge (USA). School of Biomedical Sciences
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 5114391
• Report Number(s): CONF-780227-5
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
560301 -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALDEHYDES
ALKYLATING AGENTS
AMINES
ANIMAL CELLS
ANIMALS
ANTIMITOTIC DRUGS
AROMATICS
AZINES
BIOASSAY
BIOLOGICAL EFFECTS
BIOLOGY
BODY
CARCINOGENS
CHROMOSOMAL ABERRATIONS
CONDENSED AROMATICS
CYTOLOGY
DRUGS
EMS
ESTERS
FEMALE GENITALS
FLUORENE
FORMALDEHYDE
GENETIC EFFECTS
GENETICS
GONADS
HAMSTERS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
MAMMALS
MUTAGENESIS
MUTAGENS
MUTATIONS
NITROGEN MUSTARD
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OVARIES
PYRIDINES
QUINOLINES
RODENTS
SULFONIC ACID ESTERS
TOXICITY
VERTEBRATES