On the bioactivation and genotoxic action of fluoranthene.

Fluoranthene (FA) was studied with respect to possible mechanisms of its high mutagenicity but low carcinogenicity, in comparison with the corresponding properties of benzo[a]pyrene (BaP), and with regard to the synergism of these two compounds shown by van Duuren and Goldschmidt (J Natl Cancer Inst 56, 1976, 1237). FA and BaP activated by S9 from Aroclor 1254 (PCB)-treated rats induce HPRT mutations in CHO cells with about equal effectiveness at the same exposure doses, which also lead to the same frequencies of repairable DNA adducts, enzyme-induced strand breaks being used as an indirect measure of adducts to DNA. FA was also shown to be an efficient inducer of SCE in human peripheral lymphocytes cocultivated with PCB-treated HepG2 cells or with liver cells from PCB-pretreated rats.

Increased frequency of acetaldehyde-induced sister-chromatid exchanges in human lymphocytes treated with an aldehyde dehydrogenase inhibitor.

Acetaldehyde, the first metabolite of ethanol oxidation, in concentrations ranging from 100 microM to 400 microM caused a dose-dependent linear increase in the frequency of sister-chromatid exchanges (SCE) in cultured human peripheral lymphocytes. The SCE frequency was on an average 2-fold higher when the cells were exposed to the acetaldehyde after 24 h incubation instead of at the time of mitogen stimulation (0 h). When acetaldehyde was added together with the potent aldehyde dehydrogenase inhibitor 1-aminocyclopropanol (0.

Genotoxic effects of ethylene oxide and propylene oxide: a comparative study.

The two alkylating agents ethylene oxide (EO) and propylene oxide (PO) were compared for genotoxic effectiveness in various test systems. The study was undertaken partly to shed light on the difference between the compounds found after chronic exposure of monkeys (Lynch et al., 1984) where EO but not PO was able to induce SCE and chromosomal aberrations.

Induction of sister-chromatid exchanges by direct and indirect mutagens in human lymphocytes, co-cultured with intact rat liver cells. Effect of enzyme induction and preservation of the liver cells by freezing in liquid nitrogen.

An in vitro assay system using intact rat hepatocytes and human peripheral lymphocytes is described which has been developed with the aim of bringing test conditions closer to in vivo conditions, thereby broadening the available battery of simple in vitro assays. A culture vessel, which contains an inner chamber with a semipermeable bottom, has been designed to allow easy removal of the hepatocytes. Determination of sister-chromatid exchange rate was used as the experimental end point.

Activation of human T cells by neuraminidase-galactose oxidase-treated erythrocytes involving CD2 (T11) and its complementary structure.

Human T lymphocyte proliferation induced by neuraminidase-galactose oxidase (NAGO)-treated autologous erythrocytes (HENAGO) plus polyethylene glycol (PEG) has previously been shown to be independent of accessory cells. Here, we show that the response to HENAGO + PEG was accompanied by interleukin 2 (IL-2) release and was inhibited by anti-IL-2 and anti-IL-2 receptor antibodies. HENAGO alone initiated DNA synthesis together with phorbol ester (12-O-tetradecanoyl-phorbol-13-acetate; TPA).