title: Late mitosis/early G1 phase and mid-G1 phase are not hypersensitive cell cycle phases for neoplastic transformation of HeLa x skin fibroblast human hybrid cells induced by fission-spectrum neutrons.
abstract: 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-spectrum neutrons compared to that at 10.7 cGy/min has been confirmed with the use of alkaline phosphatase chromogenic substrate Western Blue staining 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 period in the cell cycle in which cells are significantly more sensitive to neoplastic transformation than in the rest of the cell cycle, as has been postulated previously (Rossi and Kellerer, Int. J. Radiat. Biol. 50, 353-361, 1986; Brenner and Hall, Int. J. Radiat. Biol. 58, 745-758, 1990; Elkind, Int. J. Radiat. Biol. 59, 1467-1475, 1991), we compared the sensitivity of late mitotic/early G1-phase and mid-G1-phase cells with that of asynchronous cells. The rationale for examining these particular cell cycle phases was based on the fact that mitosis has been hypothesized to be a candidate for the extremely sensitive period, and on a preliminary report that mid-G1-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 G1-phase nor mid-G1-phase cells are significantly more sensitive than asynchronous cells. Further, the dependence on the phase of the cell cycle for neoplastic transformation of CGL1 cells induced by fission-spectrum neutrons is different from that previously demonstrated for gamma radiation, where late-mitotic cells were approximately five times more sensitive than mid-G1-phase and asynchronous cells (Redpath and Sun, Radiat. Res. 121, 206-211, 1990).
authors.affiliation: Department of Radiation Oncology, University of California, Irvine 92717.
authors.forename: J L
authors.initials: JL
authors.lastname: Redpath
authors.forename: R J
authors.initials: RJ
authors.lastname: Antoniono
authors.forename: C
authors.initials: C
authors.lastname: Sun
authors.forename: H M
authors.initials: HM
authors.lastname: Gerstenberg
authors.forename: W F
authors.initials: WF
authors.lastname: Blakely
mesh_terms: D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects*; D004247:DNA / Q000032:analysis / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005214:Fast Neutrons; D005347:Fibroblasts; D005434:Flow Cytometry; D016193:G1 Phase / Q000528:radiation effects; D005720:Gamma Rays; D006367:HeLa Cells; D006801:Humans; D006822:Hybrid Cells / Q000528:radiation effects; D008938:Mitosis / Q000528:radiation effects; D012867:Skin; D013194:Staining and Labeling
chemical_list: D004247:DNA