Clode S A, Anderson D
British Industrial Biological Research Association, Carshalton, Surrey, Great Britain.
Mutat Res. 1988 Jul-Aug;200(1-2):249-54. doi: 10.1016/0027-5107(88)90089-9.
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.
已知碱基和核苷过量或缺乏会在体外产生遗传效应，本实验室在体内也发现核苷胸苷有类似效应。为证实这一效应，并查看碱基腺嘌呤是否也会出现这种情况，通过腹腔注射将胸苷和腺嘌呤给予雄性小鼠，4周和5周后检查精子的头部形状异常情况。处理过的雄性小鼠还与未处理的雌性小鼠交配，以产生F1代。F1代雄性小鼠在14周龄时接受精子形态分析。在给予腺嘌呤的F0代雄性小鼠中，异常精子的频率呈剂量相关增加，给予胸苷的组也有增加，证实了本实验室先前的研究结果。在F1代中，来自处理过的雄性小鼠的精子异常数量增加的小鼠比例高于对照组。在用胸苷处理的小鼠进行的微核试验中，有丝分裂延迟，微核略有增加，这表明核苷库失衡可能是体内体细胞染色体损伤的原因。因此，可以认为在体内能够证明与体外产生的效应类似的效应。此外，精子形态分析结果表明这种损伤是可遗传的。
