Mutagenesis and cell transformation of mammalian cells in culture by chemical carcinogens

Journal Article · Sun Jan 01 04:00:00 EST 1978 · J. Environ. Pathol. Toxicol.; (United States)

OSTI ID:6227609

Huberman, E

In the process of in vitro cell transformation, normal cells, which have an oriented pattern of growth and a limited life span in vitro and which are not tumorigenic, are converted into cells that have a hereditary random pattern of growth, the ability to grow continuously in culture, and the ability to form tumors. Such heritable phenotypic changes may arise from alterations in gene expression due to somatic mutations after interaction of the carcinogen with cellular DNA. Our studies have indeed shown (a) that metabolically activated carcinogenic polycyclic hydrocarbons which have been shown to bind to cellular DNA induce somatic mutations in mammalian cells; (b) that there is a relationship between the degree of mutant induction and the degree of carcinogenicity of the different hydrocarbons tested; and (c) that the somatic mutations were induced by metabolites rather than by the hydrocarbons themselves. In the case of benzo(a)pyrene (BP), a very common carcinogenic polycyclic hydrocarbon, its 7,8-diol-9,10-oxide was identified as the major mutagenic and cell-transforming metabolite. Based on these studies, it was possible to estimate the genetic target size for cell transformation by comparing in the same cells the frequency of cell transformation and mutation for ouabian resistance (which is presumably due to a mutation at one locus) induced by BP and by one of its major metabolites. The results indicated that the target size for transformation is 20 times larger than that determined for ouabain resistance. This suggests that cell transformation, as determined by a hereditary pattern of cell growth, may be due to a mutation and that this mutation can occur in one out of a small number of the same or different genes.

• Research Organization: Oak Ridge National Lab., TN
• OSTI ID: 6227609
• Journal Information: J. Environ. Pathol. Toxicol.; (United States), Journal Name: J. Environ. Pathol. Toxicol.; (United States) Vol. 2; ISSN JEPTD
• 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.
ANIMAL CELLS
AROMATICS
BENZOPYRENE
BIOLOGICAL EFFECTS
CARCINOGENS
CELL CULTURES
CONDENSED AROMATICS
DISEASES
DNA
GENES
HYDROCARBONS
IN VITRO
METABOLISM
MORPHOLOGICAL CHANGES
MUTAGENS
MUTATIONS
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PHENOTYPE
ULTRASTRUCTURAL CHANGES