Kazuo Umezawa

Induction of sister chromatid exchanges by nicotinamide in Chinese hamster lung fibroblasts and human lymphoblastoid cells.

Summary Nicotinamide, which occurs naturally, produced sister chromatid exchanges in Chinese hamster lung fibroblasts and human lymphoblastoid cells. The inductions were dose-dependent with concentrations of 1.0–10.0 mM nicotinamide. Elastatinal, a protease inhibitor that has been reported to suppress induction of sister chromatid exchanges by N-methyl-N′-nitro-N-nitrosoguanidine, did not suppress induction of sister chromatid exchanges by nicotinamide in these cell lines.

Morphological transformation, sister chromatid exchange and mutagenesis assay of betel constituents

Betel quid, a masticatory widely used in Sri Lanka, consists of Jaffna tobacco, the nuts and leaves of betel plants and calcium hydroxide. An ethyl acetate extract of Jaffna tobacco induced morphological transformation of hamster embryo cells. The extract also induced sister chromatid exchanges inn virally transformed and phytohaemagglutinin (PHA)-stimulated human lymphocytes. The induction of sister chromatid exchanges was potentiated by addition of rat liver homogenate. The extract did not induce ouabain-resistant mutation of V79 cells. Extracts of betel nuts and leaves gave negative results in assay of morphological transformation, sister chromatid exchange and mutagenesis.

Inhibition of epidermal growth factor receptor functions by tyrosine kinase inhibitors in NIH3T3 cells.

Epidermal growth factor (EGF) induces transformed phenotypes in EGF receptor‐overexpressing NIH3T3 (ER12) cells. Tyrosine kinase inhibitors such as erbstatin and its stable analogue methyl 2,5‐dihydroxycinnamate inhibited the EGF‐induced phenotypes changes in these cells; while 5′‐O‐methylerbstatin, an inactive analogue, did not. Methyl 2,5‐dihydroxycinnamate inhibited intracellular tyrosine kinase activity in EGF‐treated ER12 cells. Methyl 2,5‐dihydroxycinnamate also delayed the EGF‐induced DNA synthesis from the quiescent phase ER12 cells without showing irreversible cytotoxicity. It inhibited the DNA synthesis most efficiently at the early G1 phase. Thus, tyrosine kinase inhibitors may modify malignant phenotypes in EGF receptor‐overexpressing neoplasms.

Inhibition of histidine decarboxylase and tumour promoter-induced arachidonic acid release by lecanoric acid analogues

Lecanoric acid analogues containing benzanilide structure inhibited histidine decarboxylase and arachidonic acid release from the cell membrane phospholipids induced by a tumour promoter, 12-O-tetradecanoylphorbol-13-acetate. But they did not inhibit cellular binding of phorbol-12,13-dibutylate. Lecanoric acid analogues also inhibited prostaglandin synthetase and delayed-type hypersensitivity responses against sheep red blood cells in mice. Thus, lecanoric acid analogues antagonized several enzymic and cellular effects of the tumour promoter.

Enhancement of fibronectin expression by herbimycin A

Herbimycin A specifically inrreased the level of fibronectin mRNA in Rous sarcoma virus-infected rat kidney cells, and the time course of fibronectin expression was found to be closely related to that of morphological change induced by herbimycin A.

Enhancement of the mutagenicities of N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea by glucose.

The mutagenicity of N-methyl-N-nitro-N-nitrosoguanidine to Salmonella typhimurium hisG46 was enhanced by pre-incubating the chemical with bacteria in sodium phosphate buffer. Addition of glucose (to 15 mM) to the pre-incubation mixture further enhanced the mutagenicity. Pre-incubation with glucose also increased the mutagenicity of N-methyl-N-nitrosourea. Fructose, galactose, pyruvate and succinate also enhanced the mutagenicity of N-methyl-N-nitro-N-nitrosoguanidine. The effect of glucose was observed with S. typhimurium strains hisG46, TA1975, TA1950, TA1535 and TA100.

In vitro transformation of hamster embryo cells by betel tobacco extracts

Abstract In vitro carcinogenicity of betel tobacco extracts was examined in a transformation assay with cryopreserved hamster embryo cells. The ethanol extract induced a transformed colony at 100 μg ml and the ethyl acetate extract induced 2 transformed colonies at 5 μg ml and 2 at 100 μg ml .

Inhibition of tumor promotion by a lecanoric acid analogue

3′, 5′-Dichloro-2,4′-dihydroxybenzanilide, an inhibitor of histidine decarboxylase, inhibited skin tumor promotion induced by 12-O-tetradecanoylphorbol-13-acetate in mice.

Enhancement of haemolysis and cellular arachidonic acid release by pyrrolomycins

Summary The chlorine-containing antibiotics pyrrolomycins enhanced haemolysis induced by melittin and trichomycin. Pyrrolomycins alone were not haemolytic. Pyrrolomycin B enhanced arachidonic acid release from cellular membrane phospholipids induced by melittin and trichomycin. Pyrrolomycin B also potentiated the action of tumour promoters such as 12-O-tetradecanoylphorbol-13-acetate and teleocidin B on arachidonic acid release, but did not inhibit cellular binding of phorbol ester. Pyrrolomycin B increased hexose transport of cultured cells.