CORRELATED MUTAGENESIS OF BCL2 AND HPRT LOCI IN BLOOD-LYMPHOCYTES

In vivo measurement of human somatic mutations may be a valuable biodo simeter of exposure to carcinogens and of cancer risk. We have surveye d translocations at the bcl2 locus in B lymphocytes, and mutations at hprt in T lymphocytes, in 120 individuals with varying exposure to rad on and cigarette smoke. bcl2 t(14:18) translocation is the commonest c hromosomal alteration observed in non-Hodgkins lymphoma (NHL). We obse rved a significantly larger range of bcl2 translocation Frequency (ran ge: 0-372 x 10(-6), median: 1.9 x 10(-6)) than of hprt mutation Freque ncy (range: 0-76.4 x 10(-6) median: 11.1 x 10(-6)),which is likely the result of clonal proliferation of deathless B cell mutants. We observ ed that the frequencies of these two distinct lymphocytic mutations ar e significantly correlated. Although some of the correlated variation is explained by age, a significant correlation of bcl2 mutagenesis per sists after age adjustment. Correlated mutagenesis at distinct loci in distinct cell types could be explained by the existence of a mutator phenotype or by variation in exposure to environmental mutagens. NHL i s commoner in men than in women, and our data indicate a trend toward higher bcl2 mutagenesis in males than females. There is mounting epide miological evidence For a worldwide increase in NHL, which may have an environmental basis; molecular epidemiological analysis of bcl2 mutag enesis in exposed populations might be especially relevant to the iden tification of putative environmental causes. Given the relative ease o f the bcl2 assay versus the hpri assay, and the consistency with which data are reproduced from laboratory to laboratory, it is likely that the bcl2 assay will be soon added to the array of assays used in human mutational surveillance. (C) 1997 Wiley-Liss, Inc.