The effects of multiple treatments with the alkylating agent chlorambucil on testicular function in the adult Wistar rat were evaluated. Weekly treatment with doses of 2.5, 5, or 10 mg/kg produced no effect either on spermatogenesis or Leydig cell function. In contrast, doses of 8 or 10 mg/kg administered twice weekly induced damage to both spermatogenesis and probably the Leydig cells. A dose-dependent decrease in spermatogonial stem-cell survival was observed with these two regimens, as assessed by counts of repopulating tubule cross sections. Although serum testosterone remained unchanged, possible Leydig cell damage was indicated by an approximate twofold increase in serum LH following treatment with either 8 or 10 mg/kg of chlorambucil twice weekly. The present results demonstrate that multiple treatments with cytotoxic drugs can be used to model the testicular damage observed in man.

The response of the testes of two strains of adult rats (Sprague-Dawley and Wistar) to graded single doses and split doses of 230 kVp X rays has been investigated. A marked difference was noted between the strains in the response of the clonogenic spermatogonia to irradiation, as measured histologically by the repopulation index. Single-dose response curves derived for these cells in the Sprague-Dawley strain had a much larger shoulder (up to about 4-5 Gy) than for the Wistar (less than 2 Gy). Split-dose studies revealed that this difference may partly be explained by a greater repair capacity in the cells of the Sprague-Dawley strain. Changes in serum FSH concentrations mirrored the changes in clonogenic spermatogonial survival following split doses of radiation.

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Sperrnatogenic stem-cell survival after gamma-irradiation has been investigated in the adult Wistar rat. Single doses of 4.5 and 9 Gy gamma-rays were administered to the testes of rats who received arachis oil (0.1 mlil0O g body weight) or testosterone enanthate (240 pgi100 g body weight) subcutaneously three times weekly for 6 weeks prior to radiation and during the week in which the radiations were given. A mean percentage of regenerating seminiferous tubule cross-sections of 32.45% and 7.26% was found in the testes of androgen-pretreated rats at 8 weeks after 4.5 and 9 Gy, respectively. Similar values (33.4% and 6.2%) were obtained in arachis oil-pretreated controls. We therefore conclude that protection of rat spermatogenesis from single doses of gamma-rays cannot be achieved by androgen pretreatment.