Armin Basler

Evaluation of the SOS chromotest

In the present investigation, the SOS chromotest with E. coli PQ37 was evaluated. The potential to identify different kinds of bacterial mutagens was examined. 124 chemicals of different chemical classes were tested. Their responses in the SOS chromotests were compared to reported test results obtained with the Ames test.

Epoxides: comparison of the induction of SOS repair in Escherichia coli PQ37 and the bacterial mutagenicity in the Ames test

The genotoxicity of 51 epoxides is studied with the SOS-Chromotest using Escherichia coli PQ37 as tester strain. The results obtained with this test system are compared with results of the Ames test. Out of 51 epoxides, 39 are shown to be mutagenic in Salmonella typhimurium whereas only 27 mutagenic epoxides induced the SOS response in Escherichia coli PQ37.

The restriction endonuclease Alu I induces chromosomal aberrations and mutations in the hypoxanthine phosphoribosyltransferase locus, but not in the Na+/K+ ATPase locus in V79 hamster cells

The restriction endonuclease Alu I induces chromosomal aberrations and mutations in the hypoxanthine phosphoribosyltransferase (HPRT) locus as measured by 6-thioguanine resistance (TGr) in V79 hamster cells. Alu I does not induce mutations in the Na+/K+ ATPase locus as measured by ouabain resistance (OUAr). The data are interpreted to mean that most if not all Alu I-induced TGr mutations represent chromosomal aberrations.

Screening of the food additive propionic acid for genotoxic properties

Genotoxic properties of the food additive propionic acid were analysed using the Escherichia coli DNA repair assay, the SOS chromotest, the Salmonella/microsome mutagenicity test, the sister chromatid exchange test in vitro and the micronucleus test in vivo. All tests except the DNA repair assay with E. coli yielded negative results. These data support other evidence that propionic acid is not mutagenic and that genotoxic events are unlikely to be the cause of forestomach lesions in rats fed propionic acid in the diet (Griem, Bundesgesundheitsblatt 1985, 28, 322).

Enhancement and inhibition of benzo[a]pyrene-induced SOS function in E. coli by synthetic antioxidants

8 antioxidants were tested in the SOS chromotest for induction of SOS function and for modulation of benzo[a]pyrene-induced SOS function. None of the antioxidants leads to increased beta-galactosidase activity by itself. Butylated hydroxytoluene at concentrations between 10(-5) M and 3 X 10(-4) M enhances benzo[a]pyrene-induced SOS function at benzo[a]pyrene concentrations between 10(-6) M and 3 X 10(-5) M. Butylated hydroxyanisole, ethoxyquin, propyl gallate and octyl gallate also slightly enhance benzo[a]pyrene-induced SOS function at concentrations up to 3 X 10(-4) M though to a lesser degree than butylated hydroxytoluene. Dodecyl gallate, vitamin C and alpha-tocopherol do not increase benzo[a]pyrene action. In concentrations exceeding 3 X 10(-4) M all synthetic antioxidants tested but not vitamin C and alpha-tocopherol decrease beta-galactosidase activity both in the absence and, more extensively, in the presence of benzo[a]pyrene. Preliminary data suggest that the apparent suppression of benzo[a]pyrene-induced SOS function is not due to an effect on the formation of benzo[a]pyrene metabolites by the metabolizing system used.

Induction of DNA-repair synthesis in primary rat hepatocytes by epoxides

The genotoxicity of 10 epoxides was investigated in the UDS test with primary rat hepatocytes. The sensitivity of the assay was demonstrated using 2-acetylaminofluorence. The epoxides 1,2-epoxyoctane, 1,2-epoxydecane, epoxycyclooctane, epoxycyclododecane, (+)-limoneoxide, alpha-pinaneoxide, transstilbeneoxide, and cis-2,3-epoxysuccinic acid, which are known to be non-mutagenic in the Ames test, as well as the bacterial mutagen, 1,2-epoxyphenoxypropane did not induce UDS in primary hepatocytes of the rat. However, a positive UDS response obtained with glycidyltrimethylammonium chloride showed that metabolic inactivation of the oxirane ring in hepatocytes is influenced by further structural substituents.

Culture of pre-implantation chinese hamster (Cricetulus griseus) embryos in vitro

Pre-implantation embryos from Chinese hamsters (Cricetulus griseus) were cultivated under completely defined conditions. The embryos were placed in drops of chemically defined medium under liquid paraffin and cultured in an atmosphere of 10% CO2 in air. By this method, development will proceed in vitro from the two-cell stage up to the blastula within 72 h. It is possible to stop the cultivation at different stages of development, to fix the embryos and analyse the chromosomes. The method described in detail seems to be appropriate for examination of the induction of genetic defects during the first days of embryogenesis.

Transplacental and direct exposure of mouse and marmoset to ethylnitrosourea: Analysis of chromosome aberrations

The effect of ethylnitrosourea (ENU) on chromosomes of mouse bone marrow cells and transplacentally exposed embryonic liver cells was investigated. Chromosome aberrations were found to be dose- and time-dependent. The maximum damage was seen 6 h after the exposure. Chromosome aberrations were also induced in bone marrow cells and lymphocytes of marmosets (Callithrix jacchus) directly exposed to ENU. Aberrations did not, however, occur in offspring whose mothers were treated with ENU before conception. Furthermore, chronic transplacentally exposed offspring have been analyzed. The frequency of chromosome aberrations was not increased in their lymphocytes and fibroblasts. The elimination of chromosome aberrations during embryogenesis is discussed.

Vinyl chloride: an example for evaluating mutagenic effects in mammals in vivo after exposure to inhalation

As part of a programme of investigations on the mutagenic effects in mammals in vivo after inhalation of environmental chemicals, the effects of the industrial compound vinyl chloride (VC) was analysed.Chinese hamsters were exposed to 1.25%, 2.5% or 5% (v/v) VC in air for 6, 12 or 24 h. Bone marrow chromosomes were analysed for induced chromosome aberrations and sister-chromatid-exchanges (SCEs) 26 h after beginning of exposure.The frequency of VC-induced chromosome aberrations and SCEs both depend on dose and length of exposure. The highest measured effects were 33.25 SCEs/cell after an exposure to 2.5% VC for 24 h and 25.7% metaphases with aberrations, when exposed to 5% VC for 24 h.ZusammenfassungIm Rahmen eines Programmes zur Untersuchung mutagener Effekte beim Säuger in vivo nach Inhalation von Umweltschadstoffen wurde Vinylchlorid (VC) untersucht.Chinesische Hamster wurden mit 1,25%, 2,5% oder 5% (v/v) VC in Luft für 6, 12 oder 24 h begast. Chromosomen des Knochenmarks wurden 26 h nach Begasungsbeginn präpariert und auf induzierte Chromosomenaberrationen und Schwesterchromatid-Austausche (SCEs) hin untersucht.Die Häufigkeit VC-induzierter Chromosomenaberrationen und SCEs hängt sowohl von der Dosis ab, als auch von der Expositionszeit. Die höchsten ermittelten Werte waren 33,25 SCEs/Zelle nach einer 24stündigen Begasung mit 2,5% VC und 25,7% Metaphasen mit Aberrationen nach 24stündiger Begasung mit 5% VC.

Bisherige Untersuchungen mit Äthylnitrosoharnstoff — Literaturbefunde —

Athylnitrosoharnstoff (ENU) ist ein Nitrosamid. Bei physiologischem pH-Wert zerfallt ENU mit einer Halbwertzeit von t1/2 <8 min zu reaktiven Ionen. Dazu sind keine enzymatischen Reaktionen notwendig. Das letztlich wirksame Produkt ist das elektrophile Athyl-Kation CH3 -CH 2 + -. Dieses sehr reaktive Ion alkyliert nukleophile Zentren in Proteinen und Nukleinsauren, bevorzugt Phosphatgruppen und Sauerstoff- und Stickstoff- Atome der Nukleinsaurebasen. Diese alkylierenden Reaktionen sind verantwortlich fur die Wirkungen von ENU (DRUCKREY et al., 1967; RAJEWSKY, 1980).