The induction of specific-locus mutations and sister-chromatid exchanges by 5-bromo- and 5-chloro-deoxyuridine

The induction of 6-thioguanine-resistant (TGr) mutants and sister-chromatid exchanges (SCE) by 5-bromo- and 5-chloro-deoxyuridine (BrdU and CldU) was determined with Chinese hamster ovary cells in culture. Over a concentration range of 0.5-200 microM, CldU treatment caused 3-5 times the number of SCEs found with BrdU; for example, with 10 microM CldU, 60.0 +/- 14.2 SCEs/metaphase (mean +/- S.D.) were induced, while with 10 microM BrdU, only 14.6 +/- 4.1 SCEs/metaphase were found. Despite this difference in SCE induction, both compounds were mutagenic only at concentrations greater than 50 microM, and BrdU was more mutagenic than CldU. These results indicate that SCEs and gene mutations are induced by these thymidine analogs through 2 different mechanisms.