Dk. Manchester et al., SENSITIVITY OF SOMATIC MUTATIONS IN HUMAN UMBILICAL-CORD BLOOD TO MATERNAL ENVIRONMENTS, Environmental and molecular mutagenesis, 26(3), 1995, pp. 203-212
To assess the potential effect of maternal environments on human embry
onic/fetal somatic mutation, we measured the frequencies of hypoxanthi
ne-guanine phosphoribosyltransferase (HPRT, hprt gene), mutant T lymph
ocytes (M(f)), and glycophorin A (GPA) variant erythrocybs (V-f) of bo
th allele-loss (empty set/N) and allele-loss-and-duplication (N/N) phe
notypes in umbilical cord blood. The mean hprt M(f) (1.40 +/- 1.11 X 1
0(-6), N = 66) and GPA V-f (empty set/N 4.0 +/- 2.2 X 10(-6), N = 114;
N/N 2.7 +/- 2.0 X 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 co
rd blood samples from a geographically distant population (0.64 +/- 0.
41 x 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) (0.7
0 +/- 0.49 x 10(-6)) of this selected population was consistent with t
he published report and significantly lower than that of our initial p
opulation (P < 0.03, t test; P < 0.01, Mann-Whitney U test). These res
ults indicate that there is an environmental effect related to materna
l socioeconomic status on the frequency of embryonic/fetal somatic mut
ations. Molecular analyses of hprt mutants from this cohort with eleva
ted M(f) revealed a significant decrease in the relative contribution
of gross structural mutations to the overall M(f) (25 of 38, 66% vs. 3
4 of 41, 83%, P = 0.024, chi(2) test), suggesting that the higher Mi r
esulted from an elevated level of ''point'' mutations. No individual m
aternal demographic or environmental factor was identified as contribu
ting more significantly than other any factor to the observed variabil
ity in hprt M(f) or GPA V-f. (C) 1995 Wiley-Liss, inc.