Expression of Lethal Mutations Is Suppressed in Neoplastically Transformed Cells and after Treatment of Normal Cells with Carcinogens

Recent evidence from our laboratory suggests that the fraction of cells with lethal mutations is lost from the population by apoptosis. The relationship of this process to genetic instability and carcinogenesis is unclear. To examine this, tumorigenic cell populations derived from spontaneously occurring, neoplastically transformed C3H 10T1/2 foci and from radiation-induced foci were compared with wild-type C3H 10T1/2 cell populations to determine the frequency of induction of lethal mutations postirradiation. Lethal mutations did not occur in the progeny of cells from type 3 foci derived from cultures of spontaneously occurring or radiation-induced neoplastically transformed cells but were very frequent in the progeny of irradiated wild-type cells. Normal human cells (HPV-immortalized human keratinocytes and primary human normal uroepithelium) were then treated with carcinogens or transfected with the Ha-ras oncogene to see if these carcinogenic events affected the yield of lethal mutations postirradiati...