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Correlated mutagenesis of bcl 2 and hprt loci in blood lymphocytes
Author(s) -
Liu Yafei,
Cortopassi Gino,
Steingrimsdottir Herdis,
Waugh Alastair P.W.,
Beare David M.,
Green Michael H.L.,
Robinson Derek R.,
Cole Jane
Publication year - 1997
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/(sici)1098-2280(1997)29:1<36::aid-em5>3.0.co;2-b
Subject(s) - biology , mutagenesis , genetics , mutagen , chromosomal translocation , locus (genetics) , mutation frequency , carcinogen , mutation , allele , germline mutation , phenotype , somatic cell , microbiology and biotechnology , gene
In vivo measurement of human somatic mutations may be a valuable biodosimeter of exposure to carcinogens and of cancer risk. We have surveyed translocations of the bcl 2 locus in B lymphocytes, and mutations of hprt in T lymphocytes, in 120 individuals with varying exposure to radon and cigarette smoke. bcl2 t(14: 18) translocation is the commonest chromosomal alteration observed in non‐Hodgkins lymphoma (NHL). We observed a significantly larger range of bcl 2 translocation frequency (range: 0–372 × 10 −6 , median: 1.9 × 10 −6 ) than of hprt mutation frequency (range: 0–76.4 × 10 −6 , median: 11.1 × 10 −6 ), which is likely the result of clonal proliferation of deathless B cell mutants. We observed that the frequencies of these two distinct lymphocytic mutations are significantly correlated. Although some of the correlated variation is explained by age, a significant correlation of bcl2 mutagenesis persists 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 is commoner in men than in women, and our data indicate a trend toward higher bcl 2 mutagenesis in males than females. There is mounting epidemiological evidence for a worldwide increase in NHL, which may have an environmental basis; molecular epidemiological analysis of bcl 2 mutagenesis in exposed populations might be especially relevant to the identification of putative environmental causes. Given the relative ease of the bcl 2 assay versus the hprt assay, and the consistency with which data are reproduced from laboratory to laboratory, it is likely that the bcl 2 assay will be soon added to the array of assays used in human mutational surveillance. Environ. Mol. Mutagen. 29:36–45, 1997 © 1997 Wiley‐Liss, Inc.