Correlated mutagenesis of bcl2 and hprt loci in blood lymphocytes.
In vivo measurement of human somatic mutations may be a valuable biodosimeter of exposure to carcinogens and of cancer risk. We have surveyed translocations at the bcl2 locus in B lymphocytes, and mutations at 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 bcl2 translocation frequency (range: 0-372 x 10(-6), median: 1.9 x 10(-6)) than of hprt mutation frequency (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 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 bcl2 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 bcl2 mutagenesis in exposed populations might be especially relevant to the identification of putative environmental causes. Given the relative ease of the bcl2 assay versus the hprt 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.
Liu
Y
Y
Department of Biological Sciences, Stanford University, California, USA.
Cortopassi
G
G
Steingrimsdottir
H
H
Waugh
A P
AP
Beare
D M
DM
Green
M H
MH
Robinson
D R
DR
Cole
J
J
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016296:Mutagenesis; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012737:Sex Factors; D014178:Translocation, Genetic
D019253:Proto-Oncogene Proteins c-bcl-2; D007041:Hypoxanthine Phosphoribosyltransferase