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

Nature Medicine volume 4, pages 1144–1151 (1998)Cite this article

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.

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Figure 1: DNA sequence analysis of HPRT V(D)J intron 1 and 3 breakpoint mutants.
Figure 2: Distribution analysis of HPRT mutations in cord blood T lymphocytes from newborns with and without transplacental exposure to passive maternal cigarette smoke.

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Acknowledgements

We thank H. Van Vunakis for advice with cotinine determinations, as well as H. Kendall, T. Poseno, T. Hunter and S. Lang for technical assistance. This research was supported by grant numbers 1K11HD01010 and 1R29HD35309-01A1 from the National Institute of Child Health and Human Development, 1RO1HDKA33648-01A1 from the National Instituted of Child Health and Human Development and the National Cancer Institute, Office of Aids Research, and a grant from the Charles H. Hood Foundation. DNA sequencing was done in the University of Vermont Cancer Center Multi-User Molecular Biology Facility, and was supported in part by facility grant C06-HL39475 from the National Institutes of Health. Cotinine determinations were done in the University of Vermont General Clinical Research Center Core laboratory, and were supported in part by facility grant MO1RR109 from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Pediatrics, University of Vermont, Burlington, 05405, Vermont, USA

    B.A. Finette

  2. Genetic Toxicology Laboratory, University of Vermont , Burlington, 05405, Vermont, USA

    B.A. Finette, J.P. O'Neill & R.J. Albertini

  3. Department of Medicine University of Vermont, Burlington, 05405, Vermont, USA

    J.P. O'Neill & R.J. Albertini

  4. Department of Medical Biostatistics, University of Vermont, Burlington, 05405, Vermont, USA

    P.M. Vacek

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  1. B.A. Finette
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Correspondence to B.A. Finette.

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Finette, B., O'Neill, J., Vacek, P. et al. Gene mutations with characteristic deletions in cord blood T lymphocytes associated with passive maternal exposure to tobacco smoke. Nat Med 4, 1144–1151 (1998). https://doi.org/10.1038/2640

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