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Biomedical subjects

P Maier

Publications and source records attributed to P Maier.

8 recordsLinked to original sources
PubMed1979

Influence of subcellular fractions of mammalian testes on the mutagenic activity of nitrofurans toward Escherichia coli; presence of a co-mutagen-like factor.

The activation of nitrofurans to mutagenic intermediates by testicular tissue was investigated. AF-2 and nitrofurazone were tested in a microsomal suspension assay with strain E. coli K-12 343/113 as indicator and subcellular fractions from rabbit testes. Different mutation patterns were observed in the presence or absence of testicular homogenate, indicating the presence of different mutagenic intermediates. The frequency of arg+ reversion increased proportionally to the homogenate concentration suggesting that the nitrofurans were activated by testicular components to intermediates that induced base-pair substitutions. Other experiments showed that a component of low molecular weight, present in the soluble fraction of homogenates of testes from rabbits, rats and monkeys, was responsible for the increased mutation frequency. It is concluded that this "co-mutagen-like" factor either alters the metabolism of nitrofurans in E. coli and/or promotes the formation of base-pair substitution-type mutations. This direct interaction between a nonenzymic component of mammalian testes and the mutation induction/expression process in E. coli suggests the role of co-mutagen-like factors in the sensitivity of testes to nitrofurans.

Animals↗
PubMed1978

Bone marrow and lymphocyte cytogenetics of rhesus monkeys (Macaca mulatta) treated with the clastogen Mitomycin C.

Rhesus monkeys (Macaca mulatta) were used to determine their effectiveness as experimental animals for different cytogenetic tests with mitomycin C (MC). The micronucleus test (MNT and/or chromosome analysis of blood and bone marrow were made before and/or after the treatment with mitomycin C. Thus, the controls data and treated data were obtained from the same animals. With the employed methology, the micronucleus test could not be performed on living animals. Less chromosomal damage was detected in the micronucleus test of post-mortem samples than in the chromosome analysis of bone marrow. No influence by the mutagen could be observed in lymphocyte chromosomes at any of the different times of analysis. In contrast to this, bone-marrow chromosomes seemed to be highly affected by mitomycin C at day 1, 2 and 3 after injection. However, before treatment and at day 14, 16 and 17 after treatment there was no visible increase in chromosomal aberration in bone marrow.

Animals↗
PubMed1978

Granuloma pouch assay. I. Induction of ouabain resistance by MNNG in vivo.

Growth of granulation tissue was induced in rats inside a subcutaneous air pouch by injection of croton oil. Granulation tissue, isolated and cultured in vitro, gave satisfactory and reproducible cloning efficiency of fibroblast-like cells. This experimental model system was used to study the induction of autosomal point mutations in vivo leading to ouabain resistance. For this purpose the mutagen MNNG was administered in the granuloma pouch, and the formation of ouabain-resistant clones was determined in vitro. Various application schedules, expression times in vivo and selective conditions in vitro were evaluated. The highest frequencies of ouabain-resistant clones were found when MNNG was injected into the pouch 24--48 h after induction of granulation tissue, followed by an expression time in vivo of 24--48 h. No ouabain-resistant clones were formed by cells isolated from untreated rats or from animals receiving the highest tolerated doses of MNNG per os or by intraperitoneal injection. The potential usefulness of the granuloma pouch assay for the evaluation of mutagenic and carcinogenic substances in vivo is discussed.

Animals↗
PubMed1976

Ten model mutagens evaluated by the micronucleus test.

The following ten mutagenic compounds were subjected to the micronucleus bone marrow test (MNT) in the mouse: cyclophosphamide (CTX), thiotepa (TT), vincristin (VCR), colcemid (COLC), adriamycin (AM), bleomycin (BM), cytosin arabinoside (ARA C), 6-mercaptopurine (6-MP), methotrexate (MTX) and 5-fluorouracil (5-FU). Dose-effect curves were established for all compounds. With the exception of CTX, COLC and AM, the drugs also were subjected to chromosome analyses on Chinese hamster fibroblasts in vitro. The MNT revealed loss of chromatin due to chromosome breakage and rearrangements by CTX, TT and AM, to breakage by ARA C, 6-MP, MTX and 5-FU, as well as loss of entire chromosomes caused by impairment of the spindle by VCR and COLC. With the exception of BM, the effects were demonstrable in the therapeutic dose range. The MNT, provided it is carried out by the methodology of the authors, not only reveals chromatin loss but permits important conclusions in regard to the proliferative state of the bone marrow and the specific time of action of the mutagens in the cell cycle. If arrest of the cell cycle occurs, as in the case of anti-metabolites MTX and 5-FU particularly, the routine scheme of investigation needs to be modified since micronucleated cells appear only after release of the metabolic block, i.e. after a delay of 24 h. The negative bone marrow results obtained with BM emphasize the importance of combining in vivo and in vitro tests.

Animals↗