Prevention of dual promoting effects of pentachlorophenol, an environmental pollutant, on diethylnitrosamine-induced hepato- and cholangiocarcinogenesis in mice by green tea infusion

Abstract

In order to explore a possibility that the custom of drinking green tea infusion is efficacious for reducing the carcinogenic risk of environmental exposure to pentachlorophenol (PCP), we examined the effects in a hepato- and cholangiocarcinogenesis model in mice exposed to diethylnitrosamine (DEN). In the first experiment, groups of 15 male mice were initially treated with DEN at a dose of 20 p.p.m. in the drinking water for the first 8 weeks followed by a 4 week recovery interval by PCP at concentrations of 0 (basal diet), 300 or 600 p.p.m. in the diet for 23 weeks. Further groups of animals were treated with DEN and PCP in the same manner and received 2% green tea infusion (GT) instead of the drinking water from week 10 until death. PCP exposure at the high dose promoted DEN-induced hepatocarcinogenesis, and also caused progression of cystic hyperplasias of the intrahepatic bile ducts to cholangiocellular tumors. Co-administration of GT was able to prevent the increases of incidences and multiplicities of DEN-induced hepatocellular tumors and also arrest the progression of cholangiocellular tumors. In the second experiment, co-treatment with GT in the drinking water from 1 week before 300 or 600 p.p.m. PCP treatment in the diet to the end of the experiment at week 3 in B6C3F1 male mice suppressed increases of serum ALT activities, 8-oxodeoxyguanosine levels in liver DNA and bromodeoxyuridine labeling indices of hepatocytes and intrahepatic biliary epithelial cells induced by PCP. These findings suggest that regular intake of green tea may reduce the carcinogenic risk posed by an environmental pollutant, PCP, presumably due to effects on oxidative stress.

Dose‐related changes of oxidative stress and cell proliferation in kidneys of male and female F344 rats exposed to potassium bromate

“…19,25) Since the histopathological findings and serum biochemical parameters indicate no obvious nephrotoxicity in female rats treated with KBrO 3 in the drinking water at any dose tested, oxidative stress might act via mitogenic stimulation. [42][43][44] Judging from the female data, it appears that the cell proliferation observed in male rats at 125 ppm and below might be attributed to α2u-globulin accumulation and not to oxidative stress. In other words, the increase at 250 ppm and above in the males might reflect the combined effects of the two.…”

NF-κB signaling, liver disease and hepatoprotective agents

“…Their therapeutic effects have been validated in the treatment of many cancers, including liver cancer (Chen et al, 2008a). Administration of green tea was able to prevent an increase in incidence and multiplicities of DEN-induced HCC and also arrest the progression of cholangiocellular tumors in mice (Umemura et al, 2003). Another polyphenol antioxidant curcumin, a major yellow pigment found in turmeric and derived from the root of the plant Curcuma longa Linn, has been used for centuries in indigenous medicine for the treatment of a variety of inflammatory conditions and other diseases.…”

Biological Relevance of Adduct Detection to the Chemoprevention of Cancer

“…A correlation has been observed between 8-oxo-dG levels in blood leukocytes and liver tissue in patients with chronic hepatitis B and C infections (85), which are both associated with an increased incidence of hepatocellular carcinoma. A preclinical link has been established between the ability of green tea to prevent increases in rodent hepatic 8-oxo-dG levels and its ability to prevent carcinogenesis in the biliary tract, a process induced by the environmental pollutant pentachlorophenol (86). In a preclinical study of dietary selenium designed in parallel with large-scale clinical trials of this agent in the chemoprevention of prostate cancer in men, Waters et al (66) fed sexually intact elderly beagle dogs 3 or 6 g/kg/day selenium daily for 7 months.…”