Induction of monozygotic twinning in the mouse.

Abstract

VINCRISTINE SULPHATE (Oncovin, Lilly) is a drug commonly used in the chemotherapy of acute leukaemias in children, lymphomas and certain other malignant conditions. We describe here experiments investigating the teratogenicity of this drug during the early stages of embryogenesis in the mouse. We report that a low incidence of gross anomalies was observed in fetuses on days 10 and 12 of gestation when pregnant females were treated with a single dose of this agent on the sixth, seventh or eighth day of gestation. However, contrary to expectation, a high proportion of litters from females treated on the seventh and eighth day of gestation contained at least one set of monozygotic twins. In this respect the present study is unique in that an experimental method of inducing a low but significant incidence of identical twinning in a mammal is reported. Furthermore, this work provides direct evidence regarding the comparatively late stage of embryonic development when identical twin formation may be induced in the mouse, as the most advanced stage at which twinning could be induced with vincristine was at the early headfold stage. However, the highest incidence of monozygotic twinning was obtained when pregnant females were treated on the morning of the seventh day. of gestation, when embryos would be expected to be at the advanced egg-cylinder stage. It was in this latter group that a single conjoined twin of the janiceps type (cephalothoracopagus) was obtained. The possible aetiology of monozygotic and conjoined twin formation is briefly discussed here in the light of these experimental findings.