Corpus ID: 14987481

Separate mechanisms for procarbazine spermatotoxicity and anticancer activity.

@article{Horstman1987SeparateMF,
  title={Separate mechanisms for procarbazine spermatotoxicity and anticancer activity.},
  author={Martin Horstman and Gary G. Meadows and Garold S. Yost},
  journal={Cancer research},
  year={1987},
  volume={47 6},
  pages={
          1547-50
        }
}
Procarbazine causes dose-dependent decreases in sperm count after a single i.p. injection in (C57BL/6 X DBA/2)F1 male mice. Two antioxidants, N-acetylcysteine and sodium ascorbate, administered with equimolar doses of procarbazine decreased the spermatotoxicity of procarbazine. At the highest doses of procarbazine (400 mg/kg) that caused a 56% decrease in sperm count, equimolar doses of N-acetylcysteine coadministered with procarbazine caused only a 17% decrease in sperm count, and equimolar… Expand
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References

SHOWING 1-10 OF 27 REFERENCES
Procarbazine spermatogenesis toxicity: deuterium isotope effects point to regioselective metabolism in mice.
TLDR
The decrease in toxicity caused by deuterium substitution at the benzylic position, coupled with the absence of an effect with the methyl-labeled analog, indicate the requirement for regioselective oxidative metabolism of procarbazine at the Benzylic Position prior to the toxic event. Expand
Carcinogenic and other adverse effects of procarbazine in nonhuman primates.
TLDR
A number of the toxic effects of procarbazine seen in humans were seen in this series of monkeys, including vomiting and myelosuppression, and another striking toxic effect was on the reproductive system of the males. Expand
Damaging effects of fourteen chemotherapeutic drugs on mouse testis cells.
TLDR
The cytotoxic effects of single injections of single chemotherapeutic agents on the mouse testis did not appear to be predictive of which drugs will cause long-term azoospermia in humans. Expand
Influence of supplemental ascorbate on the antitumor activity of 5-hydroxydopa, a purported cytotoxic metabolite.
TLDR
Data argue against a role for 5-hydroxydopa as a metabolically derived cytotoxic formed in situ during concurrent treatment with levodopa methylester and supplemental ascorbate. Expand
Effect of procarbazine treatment of mice on alpha-glycerolphosphate dehydrogenase activity and frequency of selected abnormalities in sperm.
The in situ activity of mitochondrial alpha-glycerol phosphate dehydrogenase (alpha-GPD) as well as 2 specific sperm abnormalities [headless and disorganization of the mitochondria assemblyExpand
In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds.
TLDR
Due to its dual role as a nucleophile and as a SH donor, NAC appears to exert protective effects by modulating glutathione metabolism and the biotransformation of mutagenic/carcinogenic compounds. Expand
Induction of unscheduled DNA synthesis in the germ cells of male mice after treatment with hydrazine or procarbazine.
TLDR
The present results with hydrazine indicate either that this compound does not reach the germ cells in sufficient amounts to produce DNA damage or that the repair system in early spermatid stages does not recognize the type of DNA damage produced by this compound. Expand
Early effects of procarbazine (N-isopropyl-L-(2-methylhydrazino)-p-toluamide hydrochloride) on rat spermatogenesis.
  • L. Parvinen
  • Biology, Medicine
  • Experimental and molecular pathology
  • 1979
TLDR
The results support the concept about the primary action of procarbazine on cellular functions other than DNA or RNA synthesis, or mechanisms involved in cell division, and may be focused specifically on the Sertoli cells. Expand
Effect of cytotoxic therapy on sexuality and gonadal function.
TLDR
For those young people who retain fertility after cytotoxic therapy, prognosis should be taken into account when counseling about parenthood is given and there is no evidence of genetic abnormalities in the offspring of people previously treated with chemotherapy or irradiation. Expand
Studies on the pathway of methane formation from procarbazine, a 2-methylbenzylhydrazine derivative, by rat liver microsomes.
TLDR
It was concluded that both the azo and hydrazone metabolites of procarbazine contribute to methane formation from the terminal methyl group of the hydrazine with theAzo derivative being the predominant source and the Hydrazone derivative being a minor source of methane. Expand
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