GENE-MUTATIONS WITH CHARACTERISTIC DELETIONS IN CORD-BLOOD T-LYMPHOCYTES ASSOCIATED WITH PASSIVE MATERNAL EXPOSURE TO TOBACCO-SMOKE

We have investigated the molecular effects of passive maternal cigaret te exposure in a newborn population and consider the possible implicat ions of the observed genetic changes in the development of neoplastic diseases in children. We present a distribution analysis of somatic mu tational events in a reporter gene, HPRT, in cord blood T lymphocytes from newborns after transplacental exposure to cigarette smoke. Analys is of 30 HPRT mutant isolates from 12 newborn infants born to mothers with no evidence of environmental exposure to cigarette smoke and 37 H PRT mutant isolates from 12 infants born to mothers exposed to passive cigarette smoke showed a significant difference in the HPRT mutationa l spectrum in those exposed in utero to cigarette smoke. The most nota ble change was an increase in 'illegitimate' genomic deletions mediate d by V(D)J recombinase, a recombination event associated with hematopo ietic malignancies in early childhood. Recent epidemiological studies of maternal and paternal cigarette smoke exposure and childhood cancer s may need to be re-interpreted, given these results.