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维生素E对瑞士小鼠顺铂细胞遗传毒性的保护作用/增强作用。

Vitamin E protection from/potentiation of the cytogenetic toxicity of cisplatin in Swiss mice.

作者信息

Choudhury R C, Jagdale M B

机构信息

Department of Zoology, Berhampur University, Orissa, India.

出版信息

J Chemother. 2002 Aug;14(4):397-405. doi: 10.1179/joc.2002.14.4.397.

Abstract

Possible protection from or potentiation of the cytogenetic toxic effects of cisplatin (CP) 5 mg/kg b.w. in mouse bone marrow, spermatogonia by three different doses of alpha-tocopheryl acetate (vitamin E) 100, 200 and 300 mg/kg, and the transmission of such effects in the male germline, were assessed. CP-induced chromosomal aberrations (CAs) in bone marrow were decreased in vitamin E pretreated mice, but significantly (P < or = 0.05) only with vitamin E 300 mg/kg. The percentages of dividing cells in bone marrow were increased in vitamin E-pretreated groups of mice, but not significantly. However, the frequency of CP-induced micronuclei (MN) in polychromatic erythrocytes (PCEs) declined significantly (P < or = 0.01) in all the vitamin E-pretreated groups of mice. In spermatogonia the CP-induced CAs were also decreased significantly by vitamin E 200 mg/kg (P < or = 0.01), and 100 and 300 mg/kg (P < or = 0.05). However, transmission of CP-induced cytogenetic toxic effects from spermatogonia to spermatocyte, resulting in the formation of aberrant primary spermatocytes, was enhanced significantly in the mice pretreated with vitamin E 100 mg/kg (P < or = 0.05) and 200 mg/kg (P < or = 0.01). But the enhancement in the transmission of such effects was not significant in the mice pretreated with vitamin E 300 mg/kg. Besides, there was no significant change in vitamin E-pretreated groups of mice in the transmission of cytogenetic toxicity of CP from spermatogonia to sperm with the manifestation of abnormal sperm morphology. Thus, vitamin E protected bone marrow and spermatogonia from the cytogenetic toxic effects of CP, particularly efficiently at the highest tested dose (300 mg/kg), but it failed to protect from the transmission of such effects in the male germline of mouse and rather potentiated them to some extent. Treatment with vitamin E, an antioxidant, might be capable of protecting noncancerous cells from the oxidative damage caused by cisplatin but it might also reduce the effects of cisplatin on cancerous cells. Thus, the benefits of antioxidant treatment during cancer chemotherapy is yet to be demonstrated clearly.

摘要

评估了三种不同剂量(100、200和300毫克/千克体重)的醋酸生育酚(维生素E)对顺铂(CP)5毫克/千克体重诱导的小鼠骨髓、精原细胞细胞遗传毒性作用的可能保护或增强作用,以及此类作用在雄性生殖系中的传递。维生素E预处理的小鼠骨髓中CP诱导的染色体畸变(CAs)减少,但仅在维生素E 300毫克/千克时显著(P≤0.05)。维生素E预处理的小鼠骨髓中分裂细胞的百分比增加,但不显著。然而,在所有维生素E预处理的小鼠组中,多染性红细胞(PCEs)中CP诱导的微核(MN)频率显著下降(P≤0.01)。在精原细胞中,维生素E 200毫克/千克(P≤0.01)、100和300毫克/千克(P≤0.05)也显著降低了CP诱导的CAs。然而,在维生素E 100毫克/千克(P≤0.05)和200毫克/千克(P≤0.01)预处理的小鼠中,CP诱导的细胞遗传毒性作用从精原细胞向精母细胞的传递显著增强,导致异常初级精母细胞的形成。但在维生素E 300毫克/千克预处理的小鼠中,这种作用传递的增强不显著。此外,维生素E预处理的小鼠组中,CP从精原细胞向精子的细胞遗传毒性传递且伴有异常精子形态表现方面没有显著变化。因此,维生素E可保护骨髓和精原细胞免受CP的细胞遗传毒性作用,在最高测试剂量(300毫克/千克)时尤其有效,但它未能保护小鼠雄性生殖系免受此类作用的传递,反而在一定程度上增强了它们。用抗氧化剂维生素E治疗可能能够保护非癌细胞免受顺铂引起的氧化损伤,但它也可能降低顺铂对癌细胞的作用。因此,癌症化疗期间抗氧化剂治疗的益处尚有待明确证明。

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