Strain-dependency of procarbazine-induced testicular toxicity

Ward, Jerry Ann; Robinson, J.; Morris, Ian D.

doi:10.1016/0890-6238(89)90037-3

Cited by 9 publications

(4 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further conclu sions are difficult to make because these experiments were complicated by the extreme variability in the response of the rat testis to procarbazine. We have previously noted this effect [20] which may be due to a genetically deter mined variability in the metabolic activation of procarba zine. An important point addressed in this study was the possibility of the pharmacological manipulations of the tes tis preserving spermatogenesis but not alleviating the induction of hereditable and nonhereditable mutations which are known to occur after radiation and cytotoxic drugs.…”

mentioning

confidence: 99%

Protection against Cytotoxic- Induced Testis Damage - Experimental Approaches

Id¹

1993

Eur Urol

View full text Add to dashboard Cite

mentioning

confidence: 99%

Protection against Cytotoxic- Induced Testis Damage - Experimental Approaches

Id¹

1993

Eur Urol

View full text Add to dashboard Cite

“…The gonadotoxic effects of the anticancer drug, procarbazine, are well documented (Sherins & De Vita, 1965;Sieber et al, 1978;Chapman, 1984;Ward et al, 1989;Pogach et al, 1993). Of the three germ cell subpopulations studied, pachytene spermatocytes were most severely affected by procarbazine treatment, their numbers being reduced by a factor of about 6 when compared to controls.…”

Section: Discussionmentioning

confidence: 99%

“…Adult male inbred piebald variegated (PVG) rats, aged 6-8 weeks, were purchased &om Harlan Olac (Oxford, UK) and housed under conventional, controlled conditions with free access to water and food. Previous studies had shown that the testes of inbred strains were more sensitive and homogeneous in their response to procarbazine damage than outbred strains (Ward et al, 1989).…”

Section: Animalsmentioning

confidence: 95%

Testicular germ cell populations in the adult rat after continuous in‐vivo testicular infusion of inhibin‐A and activin‐A

Adeeko

Dunne

Mather³

et al. 1996

Int J of Andrology

View full text Add to dashboard Cite

This study investigated the in-vivo effects of inhibin-A and activin-A on germ cell subpopulations in the adult rat testis. Each animal received a total of 2 micrograms (dose 5 ng/0.5 microliter/h) of activin, inhibin or 0.1% bovine serum albumin (vehicle control) delivered intratesticularly into the left testis via a cannula connected to an abdominal minipump implant. To establish whether the hormones exerted any effect on procarbazine-induced germ cell depletion, a single intraperitoneal dose of this agent was given to a group of the rats 24 h after the start of testicular infusion of activin or inhibin. Rats were killed 14 days later. Inhibin treatment caused a reduction in the number of round spermatids without altering serum FSH levels. In procarbazine-treated rats, infusion of inhibin reduced the number of pachytene spermatocytes and reduced blood FSH levels simultaneously. Infusion of activin had no significant effect on the numbers of germ cells, but reduced the number of dead cells in the seminiferous tubules of procarbazine-treated rats. The data would therefore suggest that the effects of inhibin and activin on the seminiferous epithelium are influenced by the testicular microenvironment, and that they are capable of influencing the growth and survival of germ cells by both FSH- and non FSH-mediated mechanisms. Further experiments are needed to identify the physiological role(s) of inhibin and activin in spermatogenesis.

show abstract

“…As cyclophosphamide is inactive upon stem cells of the rat testis (Trasler et al, 1988) another anti-tumour drug, procarbazine, was chosen. Procarbazine can produce chronic infertility associated with destruction of the germinal epithelium in man and rodents (Hilscher & Reichelt, 1968;Schilsky et al, 1980;Shalet, 1983;Hodel et al, 1984;Gradishar & Schilsky, 1988;Ward et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Prolonged suppression of spermatogenesis by oestrogen does not preserve the seminiferous epithelium in procarbazine‐treated rats

et al. 1990

View full text Add to dashboard Cite

We examined the hypothesis that induction of reversible testicular atrophy, subsequent to withdrawal of gonadotrophin support, would alleviate the testicular toxicity of the anti-cancer drug procarbazine. In rats, severe but reversible testicular atrophy and suppression of spermatogenesis were induced 56 days after the subcutaneous insertion of a silastic implant containing oestradiol-17 beta. The effect of this treatment upon the testicular toxicity of four weekly doses of procarbazine (200 mg kg-1) was examined 56 days after the termination of procarbazine/oestrogen treatment. At this time the testicular endocrine and spermatogenic functions were close to normal in rats which has received only oestradiol-17 beta. Procarbazine produced severe testicular atrophy which was associated with azoospermia and destruction of the germinal epithelium. Serum LH and FSH concentrations were raised and were associated with low serum concentrations of both testosterone and androgen-binding protein. The combination of procarbazine with the oestrogen treatment did not change any of the testicular toxicity and in some cases it appeared to be exacerbated. In contrast to these experiments other studies have indicated that the testis can be protected if spermatogenesis is reversibly suppressed by other agents which are also active via the pituitary endocrine system. The data would therefore suggest that protection is achieved either by some testicular change other than withdrawal of pituitary gonadotrophin support or that oestradiol-17 beta has additional activity which is permissive for the development of the testicular toxicity of procarbazine.

show abstract

Strain-dependency of procarbazine-induced testicular toxicity

Cited by 9 publications

References 24 publications

Protection against Cytotoxic- Induced Testis Damage - Experimental Approaches

Protection against Cytotoxic- Induced Testis Damage - Experimental Approaches

Testicular germ cell populations in the adult rat after continuous in‐vivo testicular infusion of inhibin‐A and activin‐A

Prolonged suppression of spermatogenesis by oestrogen does not preserve the seminiferous epithelium in procarbazine‐treated rats

Contact Info

Product

Resources

About