The mutagenic activity of 5-bromo-2'-deoxyuridine (BrdU) in vivo in rats

BrdU tablets were implanted subcutaneously in rats, and BrdU concentrations were determined in the serum. Within 5 hr peak concentrations of 10 micrograms BrdU/ml blood were reached. The influence of BrdU in vivo on cell cycling, DNA synthesis, spontaneous sister chromatid exchange (SCE) frequencies, and gene-mutation frequencies (6-TGr) was determined in freshly isolated cells from a subcutaneous granulation tissue. The most significant effect of BrdU in vivo was a doubling of the spontaneous 6-TGr frequency. In reconstruction experiments in vitro the mutagenic activity of BrdU applied in concentrations found in vivo was 2.5-6-fold higher. With the use of agar-coated tablets, BrdU concentrations in the blood were reduced by half, and no peak concentration was found. The differential staining of chromatids was still sufficient. Since the mutagenic effect of BrdU in vitro was found to be strongly concentration dependent, the use of agar-coated tablets is recommended in experiments in which the compound is used to demonstrate SCE in vivo.