Gene mutations with characteristic deletions in cord blood T lymphocytes associated with passive maternal exposure to tobacco smoke

Nat Med. 1998 Oct;4(10):1144-51. doi: 10.1038/2640.

Abstract

We have investigated the molecular effects of passive maternal cigarette exposure in a newborn population and consider the possible implications of the observed genetic changes in the development of neoplastic diseases in children. We present a distribution analysis of somatic mutational events in a reporter gene, HPRT, in cord blood T lymphocytes from newborns after transplacental exposure to cigarette smoke. Analysis of 30 HPRT mutant isolates from 12 newborn infants born to mothers with no evidence of environmental exposure to cigarette smoke and 37 HPRT mutant isolates from 12 infants born to mothers exposed to passive cigarette smoke showed a significant difference in the HPRT mutational spectrum in those exposed in utero to cigarette smoke. The most notable change was an increase in 'illegitimate' genomic deletions mediated by V(D)J recombinase, a recombination event associated with hematopoietic malignancies in early childhood. Recent epidemiological studies of maternal and paternal cigarette smoke exposure and childhood cancers may need to be re-interpreted, given these results.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cloning, Molecular
  • Cotinine / blood
  • DNA Nucleotidyltransferases
  • Female
  • Fetal Blood / cytology
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / genetics*
  • Infant, Newborn
  • Male
  • Maternal Exposure*
  • Molecular Sequence Data
  • Mutagenesis*
  • Polymerase Chain Reaction
  • Sequence Deletion
  • T-Lymphocytes / pathology*
  • Tobacco Smoke Pollution / adverse effects*
  • VDJ Recombinases

Substances

  • Tobacco Smoke Pollution
  • Hypoxanthine Phosphoribosyltransferase
  • DNA Nucleotidyltransferases
  • VDJ Recombinases
  • Cotinine