Relationship between somatic mutation and neoplastic transformation

Journal Article · Sat Jul 01 04:00:00 EDT 1978 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.75.7.3297· OSTI ID:5734485

Barrett, J C; Tso, P O.P.

Somatic mutation and neoplastic transformation of diploid Syrian hamster embyro cells were examined concomitantly. Mutations induced by benzo(a)pyrene and N-methly-N'-nitro-N-nitrosoguanidine were quantitated at the hypoxanthine phosphoribosyltransferase and Na/sup +//K/sup +/ ATPase loci and compared to phenotypic transformations measured by changes in cellular morphology and colony formation in agar. Both cellular transformations had characteristics distinct from the somatic mutations observed at the two loci. Morphological transformation was observed after a time comparable to that of somatic mutation but at a frequency that was 25- to 540-fold higher. Transformants capable of colony formation in agar were detected at a frequency of 10/sup -5/ to 10/sup -6/, but not until 32 to 75 population doublings after carcinogen treatment. Although this frequency of tansformation is comparable to that of somatic mutation, the detection time required is much longer than the optimal expression time of conventionally studied somatic mutations. Neoplastic transformation of hamster embryo cells has been described as a multistep, progressive process. Various phenotypic transformations of cells after carcinogen treatment may represent different stages in this progressive transformation. The results oare discussed in this context and the role of mutagenesis in the transition between various stages is considered. Neoplastic transformation may be initiated by a mutational change, but it cannot be described completely by a single gene mutational event involving a dominant, codominant, or X-linked recessive locus. Neoplastic transformation induced by chemical carcinogens is more complex than a single gene mutational process. Thus, this comparative study does not give experimental support to predictions of the carcinogenic potential of chemicals based on a simple extrapolation of the results obtained from conventional somatic muation assays.

• Research Organization: Johns Hopkins Univ., Baltimore, MD
• OSTI ID: 5734485
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 75:7; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550300* -- Cytology
560305 -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BENZOPYRENE
CARCINOGENESIS
CELL CULTURES
COMPARATIVE EVALUATIONS
CONDENSED AROMATICS
HAMSTERS
HYDROCARBONS
MAMMALS
MUTAGENESIS
MUTATION FREQUENCY
MUTATIONS
NITROSO COMPOUNDS
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOGENESIS
RODENTS
SOMATIC MUTATIONS
VERTEBRATES