Nitrosourea-induced sister chromatid exchanges and correlation to cell survival in 9L rat brain tumor cells

The ability of various nitrosoureas to induce sister chromatid exchanges (SCEs) in 9L rat brain tumor cells was investigated. Treatment of cells for 1 hr with the alkylating and cross-linking agents 1,3-bis(2-chloroethyl)-1-nitrosourea or chlorozotocin produced concentration-dependent increases in SCEs; elevations above controls were detected at concentrations of 1 microM or more. Above 0.25 mM, the alkylating agent ethylnitrosourea produced a dose-dependent increase in SCEs. Treatment with the carbamoylating agent 1,3-bis(trans-4-hydroxycyclohexyl)-1-nitrosourea did not induce SCEs. The maximum drug concentration at which SCEs are readily scored kills approximately 50% of cells. When accurate cell survival data in this dose range were obtained, a direct correlation between nitrosourea-induced cell kill, measured by a colony-forming efficiency assay, and SCE induction was found. Thus, analysis of the levels of SCE production may provide information about the efficacy of antineoplastic drugs.