LATE MITOSIS EARLY G(1)-PHASE AND MID-G(1)-PHASE ARE NOT HYPERSENSITIVE CELL-CYCLE PHASES FOR NEOPLASTIC TRANSFORMATION OF HELA X SKIN FIBROBLAST HUMAN HYBRID-CELLS INDUCED BY FISSION-SPECTRUM NEUTRONS

A two- to threefold increase in the rate of neoplastic transformation in cells irradiated at a dose rate of 0.22 cGy/min with fission-spectr um neutrons compared to that at 10.7 cGy/min has been confirmed with t he use of alkaline phosphatase chromogenic substrate Western Blue stai ning to detect foci of neoplastically transformed cells through their expression of a tumor-associated antigen, the end point of the HeLa x skin fibroblast human hybrid cell transformation assay. To investigate whether the inverse dose-rate effect is due to the existence of a per iod in the cell cycle in which cells are significantly more sensitive to neoplastic transformation than in the rest of the cell cycle, as ha s been postulated previously (Rossi and Kellerer, Int. J. Radiat. Biol . 50, 353-361, 1986; Brenner and Hall, Int. J. Radiat. Biol. 58, 745-7 58, 1990; Elkind, Int. J. Radiat. Biol. 59, 1467-1475, 1991), we compa red the sensitivity of late mitotic/early G(1)-phase and mid-G(1)-phas e cells with that of asynchronous cells. The rationale far examining t hese particular cell cycle phases was based on the fact that mitosis h as been hypothesized to be a candidate for the extremely sensitive per iod, and on a preliminary report that mid-G(1)-phase C3H 10T1/2 cells may exhibit enhanced sensitivity for neutron-induced transformation. A nominal dose of 45 cGy of fission-spectrum neutrons was delivered at approximately 10 cGy/min. The data indicate that neither late mitotic/ early G(1)-phase nor mid-G(1)-phase cells are significantly more sensi tive than asynchronous cells. Further, the dependence on the phase of the tell cycle for neoplastic transformation of CGL1 cells induced by fission-spectrum neutrons is different from that previously demonstrat ed for gamma radiation, where late-mitotic cells were approximately fi ve times more sensitive than mid-G(1)-phase and asynchronous cells (Re dpath and Sun, Radiat. Res. 121, 206-211, 1990).