Mutant Quantity and Quality in Mammalian Cells (A L ) Exposed to Cesium-137 Gamma Radiation: Effect of Caffeine

Abstract

We examined the effect of caffeine (1,3,7-trimethylxanthine) on the quantity and quality of mutations in cultured mammalian A _L human-hamster hybrid cells exposed to ¹³⁷ Cs γ radiation. At a dose (1.5 mg/ml for 16 h) that reduced the plating efficiency (PE) by 20%, caffeine was not itself a significant mutagen, but it increased by approximately twofold the slope of the dose-response curve for induction of ${\rm S}1^{-}$ mutants by ¹³⁷ Cs γ radiation. Molecular analysis of 235 ${\rm S}1^{-}$ mutants using a series of DNA probes mapped to the human chromosome 11 in the A _L hybrid cells revealed that 73 to 85% of the mutations in unexposed cells and in cells treated with caffeine alone, ¹³⁷ Cs γ rays alone or ¹³⁷ Cs γ rays plus caffeine were large deletions involving millions of base pairs of DNA. Most of these deletions were contiguous with the region of the MIC1 gene at 11p13 that encodes the S1 cell surface antigen. In other mutants that had suffered multiple marker loss, the deletions were intermittent along chromosome 11. These "complex" mutations were rare for ¹³⁷ Cs γ irradiation (1/63 = 1.5%) but relatively prevalent (23-50%) for other exposure conditions. Thus caffeine appears to alter both the quantity and quality of mutations induced by ¹³⁷ Cs γ irradiation.