In order to evaluate the tumor-initiating activity of kojic acid (KA) in mouse liver, an in vivo initiation assay in liver was performed using partially hepatectomized mice. Male ICR mice were fed on a basal diet (BD) containing 0 or 3% KA for 4 weeks, followed by distilled water (DW) containing 0 or 500 ppm phenobarbital (PB) for 13 weeks. Two weeks after the treatment with PB, two-thirds partial hepatectomy was preformed in all mice in order to enhance the regeneration and proliferating activities of the hepatocytes. In microscopic examinations, no proliferative lesion was observed in any of the groups. There were no differences in the number of gamma-glutamyltransferase-positive cells, an expected marker for preneoplastic hepatocytes in mice, between the KA + DW and the KA + PB groups. In the immunohistochemical analyses of the proliferating activity of hepatocytes, significant increases in the labeling index of proliferating cell nuclear antigen (PCNA) were observed in the BD + PB and KA + PB groups as compared to the BD + DW group; however, no significant difference in the positivity of PCNA was observed between the BD + PB and the KA + PB groups. These results of the present study suggest the possibility that KA has no tumor-initiating activity in the liver of mice.
Novel polymers having a hole transport ability were prepared by condensation polymerization of N,N‘-diphenyl-N,N‘-bis(4-methylphenyl)-(1,1‘-biphenyl)-4,4‘-diamine (TPD) and paraformaldehyde
(FA) or benzaldehyde (BzA). From NMR spectra, it is revealed that addition condensation reactions
occurred exclusively at the para positions of TPD. TPD−FA polymer was linked not only by a methylene
linkage but also by a methylene ether linkage, while TPD−BzA polymer was only linked by a methine
linkage. The glass transition temperatures of TPD−FA and TPD−BzA were 183 and 239 °C, respectively.
The drift mobility of TPD−BzA measured by a standard time-of-flight (TOF) method was found to be on
the order of 10-5 and 10-6 cm2/(V s). The multilayer EL devices were fabricated using TPD−FA and
TPD−BzA polymers as a hole transport layer and Alq as an electron transport emitting layer. In both
devices, the initial driving voltage is about 4 V, and the maximum luminance is above 10 000 cd/m2 at 14
V. It is expected that these polymers can be used as a hole transport material in the EL device.
Kojic acid (KA) has been used as a food additive for preventing enzymatic browning of crustaceans and as a cosmetic agent for skin whitening. To date, it has been reported that female B6C3F1 mice receiving 3% KA in the diet were found to develop hepatocellular tumors, but the underlying mechanism of liver tumorigenicity is still not clear. In the present experiments, in order to investigate possible liver initiation activity, partially hepatectomized male F344 rats received a single oral dose of 0, 1000 and 2000 mg/kg body weight of KA followed by dietary administration of 0.015% of N-2-acetylaminofluorene (2-AAF) for 2 weeks and a single 0.8 mL/kg body weight dose of CCl 4. Furthermore, male F344 rats were fed a diet containing 0 or 2% KA for 3, 7 and 28 days, and the 8-oxodeoxyguanosine (8-OxodG) levels in nuclear DNA were measured to examine the formation of oxidative DNA adduct and cell proliferating activities of hepatocytes in the liver. In the liver initiation assay, there were no significant differences in the number or area of glutathione S-transferase placental form (GST-P) positive foci, putative preneoplastic lesions, between the KA-treated and control groups. Cell proliferation of hepatocytes in rats given KA for 3 and 7 days was significantly increased as compared with the relevant control values, but no significant elevation in 8-OxodG levels was apparent. The results of the present study suggest that KA has neither liver initiation activity nor capability of 8-OxodG formation, but some evidences suggestive of liver tumor promoting effects in rats.
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