Germ and somatic cell abnormalities following in vivo administration of thymidine and adenine

It is known that an excess of or a depletion in bases and nucleosides produce genetic effects in vitro, and a similar effect has been found with the nucleoside thymidine in this laboratory in vivo. To confirm this effect and to see if this occurs with the base adenine, thymidine and adenine were administered to male mice by i.p. injection and the sperm examined for head-shape abnormalities 4 and 5 weeks later. Treated males also were mated to untreated females for the provision of an F1 generation. The F1 males were subjected to the sperm morphology assay when they reached 14 weeks of age. Amongst those F0 males given adenine, there was a dose-related increase in the frequency of abnormal sperm and the group given thymidine also showed increases, confirming the results of previous studies in this laboratory. In the F1 generation, the fraction of mice from treated males showing increases in numbers of abnormal sperm was greater than that of the controls. In a micronucleus test with mice treated with thymidine, mitosis was delayed and there was a marginal increase in micronuclei, suggesting that an imbalance in nucleoside pools may be responsible for chromosomal damage in somatic cells in vivo. Therefore it is considered that similar effects to those produced in vitro can be demonstrated in vivo. Furthermore, the results of the sperm morphology assay show that the damage is transmissible.