The possible role of cellular genes related to retroviruses in the process of chemical and radiation carcinogenesis.
Chemical carcinogens, radiation, and tumor promoters can not introduce new genetic information into cells. They must, therefore, call upon genes already present in the target cell. We have recently explored the possibility that these host genes share homology with specific nucleic acid sequences present in some of the known retroviruses. In one set of experiments we used a cloned DNA probe prepared from the oncogene (v-mos) of Moloney murine sarcoma virus (Mo-MSV) to examine the state of integration, methylation, and transcription of the homologous cellular oncogene (c-mos) in normal murine cells and in murine cells transformed by radiation or chemical carcinogens. We found that in the transformed cells the c-mos sequence has not undergone rearrangement within the host genome and, as in normal cells, this sequence is hypermethylated and transcriptionally silent. These results are in sharp contrast to the situation in cells transformed by Mo-MSV in which the exogenous v-mos sequence is integrated at new sites within the host genome, is undermethylated and is extensively transcribed. In related studies, we have found that another one gene, c-ras (H), also fails to show any evidence for rearrangement in carcinogen or radiation transformed C3H 10T1/2 cells. Since there is evidence that eukaryotic cells contain numerous onc genes our results do not rule out the possibility that onc genes other than c-mos and c-ras (H) may play a role in the transformation of murine cells by chemicals or radiation. Additional studies utilizing probes to other onc genes are required to evaluate this possibility.
D000818:Animals; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D007942:Leukemia, Experimental / Q000382:microbiology; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics; D009369:Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000382:microbiology; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D009857:Oncogenes / Q000187:drug effects / Q000528:radiation effects; D012190:Retroviridae / Q000235:genetics*
D002273:Carcinogens; D004273:DNA, Neoplasm; D004247:DNA