Differential DNA Damage Induced by Chemical Mutagens in Cells Growing in a Modified Selye’s Granuloma Pouch

Lee, I.P.; Zbinden, G.

doi:10.1159/000162926

Cited by 7 publications

(2 citation statements)

References 8 publications

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“…Vasantha (16) reported the inhibition of nucleic acid polymerases in parthenintreated FleLa cells. In addition to the above mechanisms of cytotoxicity, evidence is also accumulating in support of the potent alkylating nature of sesquiterpene lactones that could result in subsequent demage to DNA per se (7,8,(38)(39)(40)(41)(42). Recently, Lion et a!.…”

Section: Discussionmentioning

confidence: 99%

Toxicity of the Sesquiterpene Lactone Parthenin to Cultured Bovine Kidney Cells

et al. 1985

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The cytotoxic effect of the sesquiterpene lactone, parthenin was studied in vitro using cultured bovine kidney cells. The drug inhibited macromolecular synthesis. Fifty percent inhibitions in RNA, DNA and protein synthesis were observed when the cells were treated with parthenin at a final concentration of 1 g/ml. The cytotoxic effect of parthenin was also evident by its ability to markedly inhibit the activities of key cellular enzymes after treatment of the cells with the toxin for 24 h.

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Section: Discussionmentioning

confidence: 99%

Toxicity of the Sesquiterpene Lactone Parthenin to Cultured Bovine Kidney Cells

et al. 1985

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“…After an expression time of suitable duration granuloma cells are isolated and can be assayed for the presence of DNA single strand breaks (Lee and Zbinden 1979), chromosome aberrations (Maier, Send offprint requests to G. Zbinden at the above address 0340-5761/80/0045/0227/$ 01.20 unpublished observation), sister chromatide exchanges (Maier, unpublished observation), and for the presence of point mutations, e.g., ouabain resistance (OUA R, Maier et al 1978), and 6-thioguanine resistance (HGPRT-, Maier et al 1980). The target cell population consists of fibroblasts growing on the inside of a subcutaneous (s.c.) air pocket.…”

Section: Introductionmentioning

confidence: 99%

Granuloma pouch assay

1980

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Proliferation of granulation tissue on the inside of a subcutaneous (s.c.) air pocket was induced in rats by administration of 0.5 ml of 0.25% croton oil (granuloma pouch). Two days after induction of the granuloma, i.e., during the period of maximal cell growth, a single dose of 0.6 mg or 0.1 mg N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered into the pouch. Fibrosarcomas of various histopathological types developed in 87% of the rats receiving the high dose and in 64% of the low dose animals. The mean latency period was 47.5 and 51.7 weeks respectively. Only one local sarcoma developed in rats treated with 0.6 mg MNNG by the s.c. route, and no tumors were observed in the groups treated with 0.1 mg s.c. The appearance of local sarcomas in the granuloma pouch tissue is correlated with previously reported frequency of point mutations (OUAR and HGPRT-) induced in granuloma fibroblasts with the same doses of MNNG. Possible mechanisms explaining the marked enhancement of the carcinogenic effect of MNNG in the granuloma pouch assay are discussed.

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Unscheduled DNA synthesis in the testis, a secondary test for the evaluation of chemical mutagens

Zbinden

1980

Arch. Toxicol.

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DNA damage induced by methylmethane sulfonate, cyclophosphamide, doxorubicin and procarbazine in male germ cells was assessed in rabbits by the demonstration of unscheduled DNA synthesis (UDS), in meiotic and postmeiotic phases of maturation. Immediately after treatment by the intravenous route tritiated thymidine was injected into both testicles. Subsequently, rabbits were ejaculated serially, sperm heads were isolated and assayed for radioactivity by liquid scintillation counting. Dose-dependent UDS was demonstrated in late spermatocytes and early spermatids. High doses of hycanthone also induced UDS, but isoniazid and metronidazole had no effect. The rabbit testis UDS test takes into account metabolic and pharmacokinetic aspects of the test substances and provides information about their penetration through the blood-testicular barrier. It is therefore useful for secondary evaluation of potential mutagens. UDS induced by procarbazine was abolished by simultaneous treatment with Ara-C. Thus, the test also recognizes substances that inhibit DNA repair synthesis.

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Differential DNA Damage Induced by Chemical Mutagens in Cells Growing in a Modified Selye’s Granuloma Pouch

Cited by 7 publications

References 8 publications

Toxicity of the Sesquiterpene Lactone Parthenin to Cultured Bovine Kidney Cells

Toxicity of the Sesquiterpene Lactone Parthenin to Cultured Bovine Kidney Cells

Granuloma pouch assay

Unscheduled DNA synthesis in the testis, a secondary test for the evaluation of chemical mutagens

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