Analysis of cell variants showing differential susceptibilities to radiation- or chemical-induced neoplastic transformation: differences in their responses to growth factors.
The induction of DNA synthesis in quiescent, density-arrested Balb/c 3T3 cells is known to be controlled by the sequential action of at least two functionally distinct sets of growth factors, so-called "competence factors" and "progression factors." Here we examined this induction pathway in Balb/c 3T3 A31-I variants, which showed differential susceptibilities to radiation- and chemical-induced neoplastic transformation despite their similar susceptibilities to radiation- or chemical-induced cell killing and mutagenesis. DNA synthesis was acquired only with the exposure to progression factors in a highly susceptible cell variant (A31-1-13) whereas both competence factors and progression factors were required for a less susceptible cell variant (A31-I-1). The competent state constitutively produced by an autologous mechanism in the highly transformation-susceptible A31-I-13 cells suggests the existence of an endogenous promoter that acts for the expression of the transformed phenotype in an autocrine fashion when the cells have been initiated by radiation or chemical carcinogens. The growth factor requirements acting as a determining factor for susceptibilities to transformation are discussed.
Tatsuka
M
M
Department of Oncogene Research, Osaka University, Japan.
Orita
S
S
Kakunaga
T
T
D000818:Animals; D002460:Cell Line; D002468:Cell Physiological Phenomena; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D002477:Cells / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004351:Drug Resistance; D014644:Genetic Variation; D006133:Growth Substances / Q000494:pharmacology* / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011836:Radiation Tolerance
D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D004247:DNA