Activation of cellular oncogenes by chemical carcinogens in Syrian hamster embryo fibroblasts

Journal Article · Wed Aug 01 00:00:00 EDT 1990 · Environmental Health Perspectives; (USA)

DOI:https://doi.org/10.1289/ehp.9088175· OSTI ID:5840171

Ebert, R; Reiss, E; Roellich, G; Schiffmann, D ^[1]; Barrett, J C; Wiseman, R W ^[2]; Pechan, R

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1. Univ. of Wuerzburg (West Germany)
2. National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)

Carcinogen-induced point mutations resulting in activation of ras oncogenes have been demonstrated in various experimental systems such as skin carcinogenesis, mammary, and liver carcinogenesis. In many cases, the data support the conclusion that these point mutations are critical changes in the initiation of these tumors. The Syrian hamster embryo (SHE) cell transformation model system has been widely used to study the multistep process of chemically induced neoplastic transformation. Recent data suggest that activation of the Ha-ras gene via point mutation is one of the crucial events in the transformation of these cells. The authors have now cloned the c-Ha-ras proto-oncogene from SHE cDNA-libraries, and we have performed polymerase chain reaction and direct sequencing to analyze tumor cell lines induced by different chemical carcinogens for the presence of point mutations. No changes were detectable at codons 12, 13, 59, 61, and 117 or adjacent regions in tumor cell lines induced by diethylstilbestrol, asbestos, benzo(a)pyrene, trenbolone, or aflatoxin B{sub 1}. Thus, it is not known whether point mutations in the Ha-ras proto-oncogene are essential for the acquisition of the neoplastic phenotype of SHE cells. Activation of other oncogenes or inactivation of tumor suppressor genes may be responsible for the neoplastic progression of these cells. However, in SHE cells neoplastically transformed by diethylstilbestrol or trenbolone, a significant elevation of the c-Ha-ras expression was observed. Enhanced expression of c-myc was detected in SHE cells transformed by benzo(a)pyrene or trenbolone.

• OSTI ID: 5840171
• Journal Information: Environmental Health Perspectives; (USA), Journal Name: Environmental Health Perspectives; (USA) Vol. 88; ISSN 0091-6765; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AFLATOXINS
ANIMAL CELLS
ANIMALS
ANTIGENS
ASBESTOS
BIOLOGICAL EFFECTS
BODY
CARBONIC ACID DERIVATIVES
CARCINOGENESIS
CARCINOGENS
CELL TRANSFORMATIONS
CHEMICAL ACTIVATION
CONNECTIVE TISSUE CELLS
EMBRYONIC CELLS
FIBROBLASTS
GENE MUTATIONS
GENES
GENETIC EFFECTS
HAMSTERS
MAMMALS
MATERIALS
METHYL NITROSOUREA
MUTAGENS
MUTATIONS
NITROSO COMPOUNDS
ONCOGENES
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
RODENTS
SKIN
SOMATIC CELLS
TOXIC MATERIALS
TOXINS
VERTEBRATES