Mechanisms of suppression of neoplastic transformation in vitro by low doses of low LET radiation.
Suppression of neoplastic transformation of HeLa x skin fibroblast human hybrid cells in vitro following low doses of low linear energy transfer radiation has been reported previously. The present study represents an exploration of two hypothesized mechanisms that may underlie this observed suppression. These are the up-regulation of reduced glutathione (GSH), a known antioxidant, and induction of DNA repair activity. The hybrid cells were found to have a high endogenous level of GSH and no induction following low doses of 60 kVp X-rays was observed. Buthionine sulfoximine (BSO), a GSH biosynthesis inhibitor, completely suppressed GSH levels in both unirradiated and irradiated cells. Furthermore, there was no significant impact of BSO-induced suppression of GSH on the neoplastic transformation frequency of either unirradiated or low dose irradiated cells indicating that glutathione levels play no role in the low dose suppression of transformation frequency. To assess the possible role of DNA repair in the low dose suppression of transformation the effect of 3-aminobenzamide (3-AB), a poly-ADP-ribose polymerase (PARP) inhibitor was examined. In these experiments, there was no significant effect of 3-AB on the transformation frequency at a dose of Cs-137 gamma rays of 0.5 cGy, however, at a dose of 5 cGy there was a significant increase (P < 0.05) in the transformation frequency in the presence of 3-AB. These findings suggest that the influence of DNA repair on the low dose suppression of transformation is significant at a dose of 5 cGy, but not at the lower dose of 0.5 cGy.
D000975:Antioxidants / Q000378:metabolism; D001549:Benzamides / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism; D005720:Gamma Rays; D005978:Glutathione / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D018499:Linear Energy Transfer; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012867:Skin / Q000378:metabolism; D013997:Time Factors; D014965:X-Rays
D000975:Antioxidants; D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D019328:Buthionine Sulfoximine; C025160:3-aminobenzamide; D005978:Glutathione