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A large series of assays of the hepatocarcinogenic potential of 112 different compounds were carried out using a rapid bioassay system developed in this laboratory based on the two-step concept of hepatocarcinogenesis. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) i.p. and starting 2 weeks later were treated with test(More)
Studies were made on potential modifying effects of phenobarbital (PB) and carbazole on tumor development induced by N-bis(2-hydroxypropyl)nitrosamine (DHPN), a wide-spectrum carcinogen in rats. Effects on the lung, thyroid, kidney, bladder and liver were investigated. Male F344 rats were given 0.2% DHPN in their drinking water for 1 week and then 0.05% PB(More)
The antioxidant activity of metallothionein (MT) was investigated. Metallothionein scavenged hydroxyl radicals (HO.) to protect DNA from the oxidative attack by microsomes. This scavenging activity of MT was approximately 50 times greater than reduced glutathione (GSH) on a molar basis. However, MT did not inhibit DNA damage induced by microsomes in the(More)
We previously found by chance that N-nitrosomorpholine (NMOR) given after a multi-carcinogenic treatment induces liver carcinomas with 56% lung metastasis, and it was confirmed that hepatocellular carcinoma (HCC) with 100% lung metastasis was produced by 24-week treatment with NMOR and additional treatment with diethylnitrosamine (DEN). In the present(More)
We studied the capacity of various chemicals to promote urinary bladder cancer in male F344 rats after initiation by N-nitroso-n-butyl-(4-hydroxybutyl)amine (BBN). The rats were given initially 0.01% BBN in the drinking-water for 4 wk and then the test compound in the diet for 34 wk. Effects were judged by measuring the formation of preneoplastic lesions(More)
The fluidity of human erythrocyte membrane, and the effect of chlorpromazine at prelytic and lytic concentrations on the fluidity have been studied by using three kinds of fatty acid spin labels and measuring the temperature dependence of Mg2+-ATPase activity. The Arrhenius plot of the apparent rotational correlation time, tau c, for probes I(12,3) and(More)
The effects of hepatocarcinogens (ethionine, thioacetamide, phenobarbital), non-hepatocarcinogens [N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)] and a hepatoinhibitor [(butylated hydroxyanisole (BHA)] were compared in medium- and long-term in vivo systems. In experiment I, 2 weeks after a single injection of(More)
To investigate the pharmacokinetics of cyproheptadine (CPH) and its metabolites, the plasma concentration and urinary excretion of CPH and its detectable metabolites were determined after intravenous (i.v.) administration of parent or synthesized metabolites to rats. The plasma CPH concentration-time course was subjected to biexponential calculation(More)
The effects of sodium saccharin and caffeine on urinary bladder carcinogenesis in Wistar strain rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were studied. Animals were given 0.01% BBN as an initiator for 4 weeks and then sodium saccharin and/or caffeine as promoters for 32 weeks (Experiment I), or were treated simultaneously with 0.001%(More)
The effects of phenobarbital (PB), polychlorinated biphenyl (PCB) and sodium saccharin (SS) on hepatic and renal carcinogenesis induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN) were examined in male F344 rats. The rats were given 0.1% EHEN in their drinking water for 2 weeks and then diet containing 0.05% PB, 0.05% PCB or 5% SS for 32 weeks. In week 3,(More)