Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
Arch Toxicol. 2011 Sep;85(9):1109-20. doi: 10.1007/s00204-010-0638-1. Epub 2011 Jan 6.
In order to assess age-dependence of susceptibility to acrylamide (ACR)-induced neural and testicular toxicity, 3- and 7-week-old male SD rats were given ACR at 0, 50, 100, or 200 ppm in the drinking water for 4 weeks, and the nervous and male reproductive systems were examined histopathologically. Testicular genotoxicity was evaluated with the comet assay and the micronucleus (MN) test. Glutathione S-transferase (GST) activity and glutathione (GSH) content in the liver and testis were also measured. In both young and adult animals, neurotoxicity was evident from 100 ppm and increased in proportion to ACR intake per body weight. In the testis, marked degeneration and exfoliation, mainly of spermatids, were observed from 100 ppm limited to young animals. The comet assay revealed ACR to significantly induce DNA damage from 100 ppm in both life stages, while MNs were found only in young rats from 100 ppm. The level of GST activity in the testis of young rats at the end of experiment was significantly lower than that of adult animals, regardless of the ACR treatment. There were no life stage-related differences in GSH contents in the liver and testis. These results suggest that susceptibility to neurotoxicity might not differ between young and adult rats when exposure levels are adjusted for body weight. Regarding testicular toxicity, young animals around puberty proved more susceptible than adult animals, possibly due to their lower level of testicular GST activity than that in adult animals.
为了评估丙烯酰胺(ACR)诱导的神经和睾丸毒性对年龄的依赖性,3 周龄和 7 周龄雄性 SD 大鼠分别以 0、50、100 或 200ppm 的剂量通过饮用水染毒 4 周,随后对神经系统和雄性生殖系统进行组织病理学检查。彗星试验和微核试验用于评估睾丸的遗传毒性。还测量了肝脏和睾丸中的谷胱甘肽 S-转移酶(GST)活性和谷胱甘肽(GSH)含量。在幼龄和成年动物中,100ppm 时即可观察到神经毒性,且随着单位体重的 ACR 摄入量的增加而增加。在睾丸中,仅在幼龄动物中观察到从 100ppm 开始的明显的精子细胞变性和脱落。彗星试验表明,ACR 从 100ppm 开始即可在两个生命阶段显著诱导 DNA 损伤,而微核仅在幼龄大鼠中从 100ppm 开始出现。实验结束时,幼龄大鼠睾丸中 GST 活性的水平显著低于成年动物,无论是否进行 ACR 处理。肝脏和睾丸中的 GSH 含量在不同的生命阶段没有差异。这些结果表明,当暴露水平按体重调整时,神经毒性的易感性在幼龄和成年大鼠之间可能没有差异。关于睾丸毒性,青春期前的幼龄动物比成年动物更易受到影响,这可能是由于它们的睾丸 GST 活性水平低于成年动物。