A cytogenetic methodology to evaluate in vitro the G2-chromosomal radiosensitization induced by chemicals at non-clastogenic doses

Abstract

Efforts to identify chemicals that are likely to pose a potential cancer threat to humans have intensified in recent years. Since radiation is a well known carcinogenic and leukemogenic agent, the chemically-induced radiosensitization may have important implications for human health. In this study, we propose an experimental methodology to evaluate in vitro the G2-chromosomal radiosensitization induced by chemicals at non-clastogenic doses and elucidate the mechanism involved. The proposed approach is based on a combination of cytogenetic methods, such as the G2chromosomal radiosensitivity assay (G2-assay) and the premature chromosome condensation (PCC) via calyculin-A induction or cell fusion. The constantly growing research regarding the clastogenic and carcinogenic potential of a variety of harmful physical and chemical agents includes the monitoring of cellular alterations linked with carcinogenesis such as (i) induction of chromosomal damage, (ii) disturbances of the DNA-repair machinery, and (iii) alterations in cell-cycle control mechanisms (Luch 2002; Sakata et al. 2007). However, most assessments of possible deleterious outcomes from environmental and occupational exposures are directed mainly towards single agents (either chemicals or radiation) and thus combined effects that may cause synergism often remain unclear. Since ionizing radiation has been associated with cancer (Finch 2007), chemically-induced-chromosomal radiosensitization may escalate the risk of genetic diseases and carcinogenesis (Scott et al. 1996). In some occupational environment (e.g., diagnostic radiology laboratories), the extensive exposure to both chemicals and radiation increases