Vl. Dellarco, GENETIC ANOMALIES IN MAMMALIAN GERM-CELLS AND THEIR SIGNIFICANCE FOR HUMAN REPRODUCTIVE AND DEVELOPMENTAL RISK, Environmental health perspectives, 101, 1993, pp. 5-11
The induction of heritable mutations in germ cells represents a potent
ial health concern. This paper highlights data from mouse germ-cell mu
tagenesis studies that have implications in the assessment of reproduc
tive and developmental risks. The paper discusses the developmental an
d reproductive consequences of induced chromosomal damage (structural
rearrangements and numerical anomalies) and describes environmental ag
ents that have been shown to produce such anomalies. Additionally, fac
tors that influence the yield of genetic damage are addressed. Studies
showing that the various germ-cell stages vary in their susceptibilit
y to the induction of genetic damage are summarized. Of the chemicals
evaluated in the male mouse, most appear to have their predominant or
strongest effect on post-stem-cell stages. The differences between mal
es and females in the susceptibility to mutagens is examined. Recent s
tudies have shown that the female may be uniquely sensitive to certain
mutagens. Finally, an important aspect of mutagenic risk is not only
effects induced in developing germ cells but also the effects of envir
onmental agents during the period from fertilization through the zygot
e and the two-cell embryo. Recent work in the mouse has demonstrated t
hat exposure during these early developmental stages leads to high fre
quencies of external and visceral fetal malformations, as well as mid-
to-late gestational death.