Buchbesprechungen

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Zeitschriften

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Zeitschriften

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Zeitschriften

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Einzelreferate und Buchbesprechungen

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Die Abderhalden-Reaktion Mittels der Quantitativen „Interferometrischen Methode Nach P. Hirsch-Jena“

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Studies to elucidate the mechanism of fenarimol-induced infertility in male rats

Fenarimol (alpha-(2-chlorophenyl)-alpha-(4-chlorophenyl)-5- pyrimidinemethanol a pyrimidine carbinol fungicide, caused a dose-related decrease in male fertility in Wistar rats. The effect was particularly evident in the anatomically normal progeny of dams treated with fenarimol throughout gestation and lactation. Based on the observation that the infertility was associated with the absence of vaginal sperm at the time of mating, the effect appeared to be the result of an absence of male sexual behavior. Fenarimol does not readily cross the placenta but does concentrate in milk, reaching three- to fivefold higher concentrations than those observed in the maternal plasma. These results suggest that fenarimol might be acting to block the perinatal development of male patterns of sexual behavior which involves the action of gonadal steroids within the central nervous system (CNS). To test this hypothesis, [14C]fenarimol was administered to dams and the radioactivity measured in the brains of the neonates. Radioactivity in the hypothalamus was three- to fourfold higher and the half-life four times longer than that observed in the remainder of the brain. Since the hypothalamus is believed to play a key role in the development and expression of male sexual behavior, it appears likely that fenarimol is acting centrally to decrease male sexual behavior, thereby decreasing male fertility.     

Amplification of genes encoding human myeloid membrane antigens after DNA-mediated gene transfer

Spontaneous amplification of genes encoding two different human myeloid surface antigens was observed after DNA-mediated gene transfer of cellular DNA from the human myeloid cell line HL-60 into NIH-3T3 mouse fibroblasts. Transformed recipient cells with highly amplified expression of either of two donor membrane polypeptides, gp150 or p67, were isolated with a fluorescence-activated cell sorter (FACS), using monoclonal antibodies specific for human myeloid cells. Immunoprecipitation of enzymatically radioiodinated polypeptides from the surface of transformed NIH-3T3 cells confirmed that expression of these proteins was amplified tenfold to 20-fold in comparison to their expression on human myeloid cell lines. The cellular DNA of cloned secondary and tertiary transformants expressing high levels of gp150 and p67 contained amplified sets of DNA restriction fragments that hybridized with human repetitive DNA sequences. Cytogenetic analysis of subclones overexpressing gp150 revealed extrachromosomal double minutes (DMs), whose presence correlated with the unstable expression of the membrane polypeptide. Human sequences in gp150-positive clones did not localize to chromosomes, consistent with their association with extrachromosomal DMs. By contrast, p67-positive subclones stably expressed the antigen, and in situ hybridization to metaphase spreads demonstrated that amplified human DNA sequences were integrated into a specific marker chromosome. Cytogenetic analysis of the parental NIH- 3T3 subclone used in these studies disclosed DMs in a low percentage of metaphases, suggesting that the recipient cells have a propensity for amplifying donor DNA.