Multistep process of neoplastic transformation of normal human fibroblasts by ⁶⁰CO gamma rays and harvey sarcoma viruses

Abstract

As reported previously (Namba et al., 1985), normal human fibroblasts were transformed by 60Co gamma-ray irradiation into immortal cells with abnormal karyotypes. These transformed cells (KMST-6), however, showed a low cloning efficiency in soft agar and no transplantability. However, upon treatment with Harvey murine sarcoma virus (Ha-MSV), the cells acquired elevated clonability in soft agar and transplantability in nude mice. Ha-MSV alone, however, did not convert normal human fibroblasts into either immortal or tumorigenic cells. The Ha-MSV-transformed KMST-6 cells showed an enhanced expression of the ras oncogene, but normal and 60Co gamma-ray-transformed cells did not. Our current data suggest that gamma rays worked against normal human cells as an initiator, giving rise to chromosome aberrations and immortality, and that Ha-MSV, probably through its ras oncogene, played a role in the progression of the malignant cell population to a more malignant one showing enhanced colony formation in soft agar and tumorigenicity in nude mice.

Neoplastic transformation of immortalized human epidermal keratinocytes by ionizing radiation.

“…Cooperating cellular or viral oncogenes have been shown to induce neoplastic transformation of embryonic rodent fibroblasts (12)(13)(14)(15)(16). In addition, the combined action of y-irradiation and Ha-ras oncogene has been demonstrated to produce neoplastic transformation of human fibroblasts (17). Our ability to obtain neoplastic transformation as a result of x-ray treatment of Adl2-SV40-altered human epidermal cells provides additional support for a multistep process of neoplastic conversion.…”

Malignant transformation of human fibroblasts caused by expression of a transfected T24 HRAS oncogene.

“…Although the MSU- (19,21), who utilized KMST-6 cells. In their studies, introduction of ras oncogenes by either virus infection (18,19) or by transfection (21) resulted in cells able to form tumors in athymic mice, although, in contrast to our results with the SV40-immortalized GM0637B cells, the tumors produced with the Va2 cells did not grow progressively (18)-an important criterion for malignant transformation, along with the ability to invade.…”

Oncogenes and tumor-suppressor genes.

“…Several studies have indicated that immortalization is a rate-limiting step in the multistage process of in vitro human cell carcinogenesis (12)(13)(14). In order to develop an immortalized cell system for studies of carcinogenesis, we have infected NHBE cells with the SV40 large T antigen gene (15).…”