Abstract
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1.
Incubation of trichloroethylene, 1,1-dichloroethylene, vinylchloride, tetra-chlorocyclopentadiene, the nitroso derivatives of the pesticides Carbaryl, Prometryn, and Dodin in the presence of metabolically active mouse liver microsomes and bacteria as target cells were mutagenic, whereas tetrachloroethylene, 1,2 cis-and transdichloroethylene, hexachlorocyclopentadiene, carbontetrachloride, chloroform, halothane, trichlorofluoromethane and styrene were not activated to mutagenic species.
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2.
In a similar in vitro test system using freshly isolated human lymphocytes as target cells dimethylnitrosamine induced chromosomal aberrations.
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3.
It is concluded from the experiments that submammalian or mammalian in vitro cell systems with metabolically active liver microsomes are not only suitable to screen for chemical mutagens but to demonstrate formation of reactive intermediates, which are short lived and cannot be detected by chemical procedures.
Zusammenfassung
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1.
Trichloräthylen, 1,1-Dichloräthylen, Vinylchlorid, Tetrachlorzyklopentadien sowie die Nitrosoderivate der Pestizide Karbaryl, Prometryn und Dodin wurden von metabolisch aktiven Mäuselebermikrosomen zu reaktiven Zwischenprodukten umgesetzt, die für zugesetzte Testbakterien mutagen waren. Tetrachloräthylen, 1,2 cisund trans-Dichloräthylen, Hexachlorzyklopentadien, Tetrachlorkohlenstoff, Chloroform, Halothan, Trichlorfluormethan und Styrol zeigten im Testsystem keine Mutagenität, während Styrolepoxid ohne metabolische Aktivierung mutagen war.
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2.
In einem metabolisch aktiven System mit frisch präparierten menschlichen Lymphozyten als Testorganismen induzierte Dimethylnitrosamin Chromosomenaberrationen.
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3.
Die Untersuchungsergebnisse zeigen, daß sich metabolisierende in vitro Testsysteme mit Bakterien oder Säugetierzellen als Testorganismen nicht nur für Routineuntersuchungen zum Nachweis mutagener Umweltchemikalien eignen sondern auch zum Nachweis reaktiver Metaboliten, die aufgrund ihrer geringen Stabilität mit chemischen Methoden nicht erfaßbar sind.
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Greim, H., Bimboes, D., Egert, G. et al. Mutagenicity and chromosomal aberrations as an analytical tool for in vitro detection of mammalian enzyme-mediated formation of reactive metabolites. Arch. Toxicol. 39, 159–169 (1977). https://doi.org/10.1007/BF00343283
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DOI: https://doi.org/10.1007/BF00343283