Department of Zoology, Berhampur University, Berhampur 760 007, Orissa, India.
Environ Toxicol Pharmacol. 2006 May;21(3):254-9. doi: 10.1016/j.etap.2005.09.002. Epub 2005 Nov 8.
Apart from its own controversial cytogenotoxic effects, caffeine (CAF), one of the most commonly consumed alkaloids worldwide, is found potentiative to and so also protective from the cytogenotoxic effects of numerous chemical and physical mutagens. It also has modulated the actions of several antineoplastic agents. Additionally, it has been tested as a chemopreventive of cancer and is reportedly associated inversely with different cancer risks. Therefore, in the present study, three different sub-lethal doses of CAF, 25, 50 and 100mg/kg, were tested in mouse to assess their cytogenotoxic effects on dividing spermatogonia at 24h post-treatment, and transmission of such effects in the male germline from the primary spermatocytes and sperm at week 4 and week 8 post-treatment, respectively. CAF was found to be weakly clastogenic to mouse spermatogonia and the effects were also found transmitted in the male germline. Interestingly, such induced effects were quantitatively related to the dose of CAF tested. On the other hand, methotrexate (MTX), an antifolate antimetabolite, is prescribed frequently for the treatment of various types of cancers. However, MTX is reportedly clastogenic. Modulation of the said three different pre-treated doses of CAF on MTX 10mg/kg-induced cytogenotoxic effects, tested in the same experimental protocol, indicated that CAF pre-treatment was decreasing the MTX-induced clastogenicity in spermatogonia, and was lowering the concurrent transmission of such effects in the male germline of mice, significantly. Such decreases were related to the dose of CAF tested, i.e. higher the dose of CAF more was the decrease in the MTX-induced cytogenotoxic effects and in their transmission. The possible mechanisms that might have caused the manifestation of a weak clastogenic action of CAF on spermatogonia and in its transmission in the male germline, and the CAF modulation of MTX-induced cytogenotoxic effects in spermatogonia and in their transmission have been discussed.
除了自身具有有争议的细胞遗传毒性作用外，咖啡因（CAF）是世界上最常消费的生物碱之一，被发现对许多化学和物理诱变剂的细胞遗传毒性作用具有增效作用，因此也具有保护作用。它还调节了几种抗肿瘤药物的作用。此外，它已被测试为癌症的化学预防剂，并据报道与不同的癌症风险呈负相关。因此，在本研究中，在小鼠中测试了三种不同的亚致死剂量的 CAF（25、50 和 100mg/kg），以评估它们在 24 小时后对分裂精原细胞的细胞遗传毒性作用，并分别在 4 周和 8 周后从初级精母细胞和精子中传递这些作用在雄性生殖细胞中。CAF 对小鼠精原细胞具有弱的断裂作用，并且发现这些作用也在雄性生殖细胞中传递。有趣的是，这种诱导的作用与测试的 CAF 剂量呈定量关系。另一方面，甲氨蝶呤（MTX）是一种抗叶酸抗代谢物，常用于治疗各种类型的癌症。然而，据报道 MTX 具有断裂作用。在相同的实验方案中测试了三种不同的预先处理剂量的 CAF 对 MTX 10mg/kg 诱导的细胞遗传毒性作用的调节表明，CAF 预处理降低了 MTX 诱导的精原细胞断裂作用，并降低了同时在雄性生殖细胞中的这种作用的传递，这具有统计学意义。这种减少与测试的 CAF 剂量有关，即 CAF 剂量越高，MTX 诱导的细胞遗传毒性作用及其传递的减少就越多。讨论了可能导致 CAF 对精原细胞表现出弱断裂作用及其在雄性生殖细胞中的传递以及 CAF 对 MTX 诱导的精原细胞和生殖细胞中的细胞遗传毒性作用的调节作用的机制。
