Collaborative Work to Evaluate Toxicity on Male Reproductive Organs by Repeated Dose Studies in Rats : 14)comparison of the Effects of 2-and 4-Weeks Intravenous Administration of Etoposide

Abstract

In order to examine whether effects on male reproductive organs following 2-weeks administration of Etoposide (ET) are detectable, ET was administered intravenously once a week to rats for 2 and 4 weeks at 5 and 10 mg/kg/week. No deaths and no drug-related changes in body weight or in gross pathology were observed. However, decreased testis and/or thymus weights were noted. And histopathological examination revealed decrease and/or loss of spermatogonia and spermatocytes in the testes. It was evident that the target cells of the test article in the male reproductive organs are spermatogonia. Atrophy of the medulla and increase of immature lymphocytes in the cortex of the thymus and increase of fatty cells and increase of immature hematopoietic cells in the bone marrow were also apparent. The histological changes in the testis, thymus and bone marrow suggest that ET inhibits cellular mitosis which reflects its mechanism of action as an anticancer agent. It is concluded that effects of ET on male reproductive organs can be detected by histopathological examination of the testes after 2-weeks repeated administration.

Reversibility of the Effects of Subchronic Exposure to the Cancer Chemotherapeutics Bleomycin, Etoposide, and Cisplatin on Spermatogenesis, Fertility, and Progeny Outcome in the Male Rat

“…However, no studies have investigated the potential persistence of these effects, particularly with respect to progeny outcome, after completion of treatment. Likewise, chronic etoposide administration induced drastic alterations in spermatogenesis at high doses, but the impact of such treatment on progeny outcome remains unknown (Kadota et al, 1989; Kawaguchi et al, 2000). In addition, these studies all consisted of exposure to a single drug.…”