Cyclophosphamide: Interstrain differences in the production of mutagenic metabolites by S9‐fractions from liver and kidney in different mutagenicity test systems in vitro and in the teratogenic response in vivo between CBA and C 57 BL mice

Winckler, K.; Obe, Günter; Madle, Stephan; Kocher-Becker, Ursula; Köcher, W.; Nau, Heinz

doi:10.1002/tcm.1770070407

Cited by 8 publications

(2 citation statements)

References 23 publications

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“…Krishna et al (1987), using both in vivo and in vitro assays, found a CP-induced, dose-related increase in sister chromatid exchanges (SCE) and chromosomal aberrations in mouse bone marrow and spleen cells. In addition, Winckler et al (1987) reported an increase in point mutations in an in vitro Salmonella assay, using liver or kidney cell fractions from CP-treated mice, as well as SCE induction in human peripheral lymphocytes. Cyclophosphamide genotoxicity in the mouse has been demonstrated in vivo by use of the micronucleus assay in colonic epithelium and bone marrow and by the NA assay in bladder epithelium (Goldberg and Josephy 1987) and in anagen hair follicles (Goldberg and Josephy 1987;Schop and Goldberg 1988).…”

Section: Introductionmentioning

confidence: 95%

Nuclear aberrations in hair follicle cells of patients receiving cyclophosphamide

et al. 1990

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The toxic effect of cyclophosphamide on the proliferative cell population of hair follicles plucked from the human scalp was examined by the in vivo nuclear aberration assay. Patients participating in an independent clinical trial received oral low dose cyclophosphamide, intravenous high dose cyclophosphamide or oral placebo treatment. The percent of cells with nuclear aberrations (indicating apoptosis, a special form of cell death) and the percent of mitotic cells, in the hair matrix, were calculated for each patient before treatment and at several time points following cyclophosphamide or placebo treatment. The mean percentages of nuclear aberrations in both the treated Low dose and High dose cyclophosphamide patients were significantly higher than those for the pre-treatment and Placebo patients. The nuclear aberrations in hair follicle cells increased from pre-treatment (and Placebo) to treated Low dose and finally to treated High dose patients. The average percentage for pre-treatment samples from all patients was 0.06 +/- 0.03 SE. For 1 week and 1 month samples from Low dose patients it was 0.35 +/- 0.08 SE, and for combined 2,3 and 4 day samples from High dose patients it was 1.08 +/- 0.12 SE. Cyclophosphamide also had a significant effect on mitosis. A decrease in mitotic activity was observed at 1 month following the initial low dose cyclophosphamide treatment and at 24 +/- 2 h following each of the first two high dose cyclophosphamide treatments. The observed increase in nuclear aberrations following low dose as well as high dose cyclophosphamide suggests that it is feasible to use the nuclear aberration assay for in vivo human genotoxicity testing, using proliferating hair follicle cells.

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Section: Introductionmentioning

confidence: 95%

Nuclear aberrations in hair follicle cells of patients receiving cyclophosphamide

et al. 1990

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“…Manson and Simons [31] found that adding S-9 directly to the culture medium interfered with limb bud development. By placing the S-9 activation system in dialysis bags, others [21,25,26] have found that this toxic effect is absent or minimal. The same is true for this system.…”

Section: Discussionmentioning

confidence: 99%

Metabolic activation in the fetal mouse salivary gland culture system with rat hepatocytes, rat S‐9, and human S‐9

Lyng

Scalf

Monteith

1991

Teratog Carcinog Mutagen

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The usefulness of an in vitro assay for embryotoxicity may depend on the availability of metabolic activation systems that will function in the culture system. The fetal mouse salivary gland has been investigated as an in vitro assay system. To see if the glands would grow in the presence of metabolic activators and if the glands would react to metabolites known to be embryotoxic, the glands were grown in the presence of cyclophosphamide (CP) and several activation systems. These included isolated rat hepatocytes, uninduced rat S-9, rat S-9 induced with 3-methylcholanthrene (3-MC), rat S-9 induced with Aroclor 1254, and human S-9. Twenty salivary glands were isolated from 13 day embryos (plug day = 0) and were grown in each treatment for 48 h. One control had no activation system of CP, one had an activation system but no CP, and three treatments had the activation system and 25, 75, or 150 micrograms/ml CP. The S-9 with cofactors and the appropriate amount of CP was contained in dialysis bags. The greatest suppression of salivary gland growth occurred in co-culture with hepatocytes activating CP. The S-9 induced by Aroclor 1254 was nearly as effective as the hepatocytes. The next most effective was a group with similar activity consisting of the uninduced rat S-9 and the three samples of human S-9. The 3-MC-induced S-9 was the least effective in suppressing growth of salivary glands. All the activation systems tested can be used with the salivary gland culture system.

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Par-4 Secretagogues in Clinical Trials

Peng

Hao

2021

Tumor Suppressor Par-4

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Cyclophosphamide: Interstrain differences in the production of mutagenic metabolites by S9‐fractions from liver and kidney in different mutagenicity test systems in vitro and in the teratogenic response in vivo between CBA and C 57 BL mice

Cited by 8 publications

References 23 publications

Nuclear aberrations in hair follicle cells of patients receiving cyclophosphamide

Nuclear aberrations in hair follicle cells of patients receiving cyclophosphamide

Metabolic activation in the fetal mouse salivary gland culture system with rat hepatocytes, rat S‐9, and human S‐9

Par-4 Secretagogues in Clinical Trials

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