Activation of cellular oncogenes by chemical carcinogens in Syrian hamster embryo fibroblasts.
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. We 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 B1. 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.
Ebert
R
R
Institute of Toxicology, University of Würzburg, Federal Republic of Germany.
Barrett
J C
JC
Wiseman
R W
RW
Pechan
R
R
Reiss
E
E
Röllich
G
G
Schiffmann
D
D
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects; D008647:Mesocricetus; D008745:Methylation; D009154:Mutation; D011519:Proto-Oncogenes / Q000187:drug effects*
D002273:Carcinogens; D004247:DNA