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Sensitivity of somatic mutations in human umbilical cord blood to maternal environments
Author(s) -
Manchester David K.,
Nicklas Janice A.,
O'Neill J. Patrick,
Lippert Malcolm J.,
Grant Stephen G.,
Langlois Richard G.,
Moore Dan H.,
Jensen Ronald H.,
Albertini Richard J.,
Bigbee William L.
Publication year - 1995
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/em.2850260304
Subject(s) - hypoxanthine guanine phosphoribosyltransferase , cord blood , umbilical cord , population , biology , andrology , fetus , allele , genetics , microbiology and biotechnology , medicine , mutant , pregnancy , gene , environmental health
To assess the potential effect of maternal environments on human embryonic/fetal somatic mutation, we measured the frequencies of hypoxanthine‐guanine phosphoribosyltransferase (HPRT, hprt gene), mutant T lymphocytes (M f ), and glycophorin A (GPA) variant erythrocytes (V f ) of both allele‐loss (ø/N) and allele‐loss‐and‐duplication (N/N) phenotypes in umbilical cord blood. The mean hprt M f (1.40 ± 1.11 × 10 −6 , N = 66) and GPA V f (ø/N 4.0 ± 2.2 × 10 −6 , N = 114; N/N 2.7 ± 2.0 × 10 −6 , N = 91) were significantly lower than those previously reported for adult populations. In addition, the hprt M f was significantly higher than that of a published study of newborn cord blood samples from a geographically distant population (0.64 ± 0.41 × 10 −6 , N = 45, P < 0.01; t test, P < 0.01, Mann‐Whitney U test). An examination of the demographic data from these two populations led to the sampling of 10 additional newborns specifically matched to the published study for maternal socioeconomic status. The hprt M f (0.70 ± 0.49 × 10 −6 ) of this selected population was consistent with the published report and significantly lower than that of our initial population ( P < 0.03, t test; P < 0.01, Mann‐Whitney U test). These results indicate that there is an environmental effect related to maternal socioeconomic status on the frequency of embryonic/fetal somatic mutations. Molecular analyses of hprt mutants from this cohort with elevated M f revealed a significant decrease in the relative contribution of gross structural mutations to the overall M f (25 of 38, 66% vs. 34 of 41, 83%, P = 0.024, x 2 test), suggesting that the higher M f resulted from an elevated level of “point” mutations. No individual maternal demographic or environmental factor was identified as contributing more significantly than other any factor to the observed variability in hprt M f or GPA V f . © 1995 Wiley‐Liss, Inc.