Biochemical studies of the rat seminiferous epithelial wave : DNA and RNA syntheses and effects of adriamycin

Parvinen, L.-M.; Parvinen, Martti

doi:10.1051/rnd:19780332

Cited by 18 publications

(7 citation statements)

References 21 publications

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“…Concentrations of drugs needed to produce similar dose-dependent reduction of DNA synthesis were 10 times higher in stage VIII-IX compared with stage V. Premitotic DNA synthesis thus is more sensitive to antracycline toxicity than premeiotic DNA synthesis, supporting the earlier observations of Parvinen and Parvinen [14]. The cytostatic drugs induced apoptosis far more rapidly than inhibition of the 3 H-thymidine incorporation.…”

Section: Discussionsupporting

confidence: 53%

“…The cell types most sensitive to this induction are spematogonia, zygotene and early pachytene spermatocytes, and meiotically dividing spermatocytes [12,13]. In vivo treatment with cytotoxic drugs has also been shown to cause inhibition of stage-specific DNA synthesis in the rat testis [14,15] and to induce DNA damage in spermatogonial cells, as measured by a micronucleus assay [16].…”

Section: Introductionmentioning

confidence: 97%

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Stage-Specific Inhibition of Deoxyribonucleic Acid Synthesis and Induction of Apoptosis by Antracyclines in Cultured Rat Spermatogenic Cells1

Jahnukainen

Hou

Parvinen

et al. 2000

Biology of Reproduction

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A rapid in vitro method has been developed to detect early effects of cytostatic drugs on rat spermatogenesis. The induction of programmed cell death (apoptosis) and changes in DNA synthesis induced by doxorubicin and idarubicin were measured in specific stages of the cycle of seminiferous epithelium including mitotic (stage V) and meiotic (stage VIII-IX) S-phase cells. The model was used to investigate the protective effect of an organic thiophosphate, amifostine, against the toxicity of antracyclines. Premitotic DNA synthesis was found to be more sensitive than premeiotic DNA synthesis to antracyclines. Idarubicin was more toxic than doxorubicin to germ cells in inducing apoptosis and suppressing DNA synthesis. Amifostine had no protective effect against doxorubicin- or idarubicin-induced inhibition of DNA synthesis. In contrast, a significant stimulation of DNA synthesis in premitotic cells by amifostine was found, suggesting that this compound may have a stimulative effect on spermatogenic stem cells. These data show that stage-specific dissection of the seminiferous tubules and their in vitro exposure to predetermined doses of drugs may give us a unique possibility to detect drug action and protection against the cytotoxicity of antineoplastic agents at the cellular level of the spermatogenic cycle.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 97%

Stage-Specific Inhibition of Deoxyribonucleic Acid Synthesis and Induction of Apoptosis by Antracyclines in Cultured Rat Spermatogenic Cells1

Jahnukainen

Hou

Parvinen

et al. 2000

Biology of Reproduction

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“…These reports indicate that B12 exhibits positive effects on male reproductive functions. Meanwhile, it was reported that doxorubicin, an anticancer agent, would inhibit nucleic acid synthesis in rat testes (29)(30)(31). Oshio et al (5) and Ozaki et al (6) reported that changes of the testicular morphology and of the parameter of sperms in the rats administered doxorubicin, such as decreases in the number of sperms and sperm motility, were alleviated by CH3-B12.…”

Section: Discussionmentioning

confidence: 99%

Effects of Vitamin B12-Deficiency on Testes Tissue in Rats.

Kawata

Takada

Morimoto

et al. 1992

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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SummaryThe state of vitamin B12-deficiency in rats was evaluated by determination of hepatic vitamin B12-dependent enzyme activities after the animals had fed on a vitamin B12-deficient soybean protein diet for 150 days. The effect of vitamin B12-deficiency on testicular tissue was also studied by morphological observations. Growth of vitamin B12-deficient rats was retarded and marked increase in urinary methylmalonic acid was observed. Vitamin B12 contents in the organs were depressed distinctly by the deficiency, especially in testes, vitamin B12 content decreased to 2.5 ng/g. Hepatic methionine synthase and methylmalonyl-CoA mutase ac tivities showed striking depression to 5% of the control rats and extreme vitamin B12-deficiency was confirmed. Testes weight also showed marked decrease together with their relative weight per 100g body weight. Mor phological observations of testes of vitamin B12-deficient rats revealed atrophy of the seminiferous tubules and aplasia of sperms and spermatids. The above results proved that vitamin B12-deficiency affected rat testes, and suggested that the rat could be the animal model for elucidation of the mechanism of B12 action on testicular functions.

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“…Fifty-six days after treatment, the reduction in sperm head counts also indicated that DX caused extensive stem-cell death. Parvinen and Parvinen (1978) determined that preleptotene and mid-pachytene spermatocytes, as well as meiotic cells, were the cells most rapidly killed in the rat with intratesticular injections of DX. With the exception of the effect on B spermatogonia, the present study most closely agrees with the study by Lu and Meistrich (1979).…”

Section: (Adriamycin)mentioning

confidence: 99%

“…Since chemotherapeutic agents fall into different categories (alkylating agents, antimetabolites, mitotic inhibitors, antibiotics, enzymes, and hormones and hormone antagonists) based on their general mechanism of action, it is reasonable to assume that the aforementioned assumption may not be correct since their mechanisms of action also differ. In fact, several recent reports indicate that damage accompanying administration of chemotherapeutic agents may extend to Serioli cells (Barcellona and Brinkley, 1973;Parvinen, 1979;Pogasch et al, 1989) and/or Leydig cells (Cooke et al, 1987;Chapman et al, 1979;Jacobson et al, 1986) or other germ-cell types (Barcellona and Brinkley, 1973;Lendon et al, 1978;Parvinen, 1979;Parvinen and Parvinen, 1978;Russell et al, 1981Russell et al, , 1983a.…”

Section: Introductionmentioning

confidence: 99%

Short‐term Morphological response of the rat testis to administration of five chemotherapeutic agents

Russell

1991

Am. J. Anat.

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As cancer survival rates improve, there is increasing concern about the adverse effects of chemotherapeutic agents on male fertility. Five chemotherapeutic agents (amethopterin, AP or methotrexate; doxorubicin, DX; cytoxan or cyclophosphamide, CP; cisplatinum, CDDP; and 5-fluorouracil, 5-FU) which belong to three different categories of chemotherapeutic agents (antimetabolite, antibiotic, alkylating agent, alkylating agent, antimetabolite, respectively) were given systemically to adult rats to determine the short-term morphological patterns of response in the testis, and the testes were examined by light microscopy. Morphological patterns of response were found to be highly characteristic for each agent, and some shared morphological responses were evident. All except one chemotherapeutic agent (5-FU) caused spermatogonial damage. Among the defects seen were probable degenerating meiotic spermatocytes (CDDP), presence of micronuclei (DX), "arrested" spermatid development (5-FU), and abnormally shaped step 15 spermatids (5-FU). Damage that could be due to the effect of an agent on the Sertoli cell was failure of sperm release (5-FU, CDDP, DX, and AP), increase in the Sertoli cell lipid (5-FU), and malorientation of step 8 spermatids (5-FU, DX). The varied patterns of damage observed are a possible explanation of why the reproductive recovery potential in cancer patients undergoing chemotherapy is variable and drug-specific.

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Biochemical studies of the rat seminiferous epithelial wave : DNA and RNA syntheses and effects of adriamycin

Cited by 18 publications

References 21 publications

Stage-Specific Inhibition of Deoxyribonucleic Acid Synthesis and Induction of Apoptosis by Antracyclines in Cultured Rat Spermatogenic Cells1

Stage-Specific Inhibition of Deoxyribonucleic Acid Synthesis and Induction of Apoptosis by Antracyclines in Cultured Rat Spermatogenic Cells1

Effects of Vitamin B12-Deficiency on Testes Tissue in Rats.

Short‐term Morphological response of the rat testis to administration of five chemotherapeutic agents

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