Biotechnology Letters, Vol.22, No.17, 1401-1406, 2000
Evaluation of hprt mutant assay as a biomarker monitoring the specific environmental mutagen
To evaluate the availability of an hprt mutant assay for monitoring a specific environmental mutagen, the mutation effects of gamma-irradiation and pentachlorophenol (PCP) on the hypoxanthine guanine phosphoriboxyl transferase (hprt) locus in a human T-cell culture system were analyzed in vitro. The assay of somatic mutation at the hprt locus did not differentiate the characteristic effect of gamma-irradiation from that produced by PCP, because both damaging agents induced the somatic mutations in a similar dose-dependent manner. Direct DNA sequencing showed that both damaging agents induced different mutation spectra in the hprt locus of T-cells. The large deletions, which account for 75% of the analyzed mutants, were induced by gamma-irradiation. By contrast, point mutations such as base substitutions rose up to 97% in the case of PCP-treated cells. It may be that 190 base pair and 444 base pair positions are hot spots induced by PCP. These results suggest that the hprt mutation spectrum can be used as a potential biomarker for assessing a specific environmental risk.
Keywords:biomarker;hprt T-cell clonal assay;hprt mutation spectrum;gamma-irradiation;pentachlorophenol