• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.46-47
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• 2001

Residents of Qidong, Peoples Republic of China, are at high risk for development of hepatocellular carcinoma, in part due to consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semi-synthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models.(omitted)

• Toxicological Research
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• v.32 no.1
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• pp.21-33
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• 2016

Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p'-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT.

• The Korean Journal of Food And Nutrition
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• v.23 no.2
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• pp.276-284
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• 2010

The effects of different dietary fatty acids on the hepatic glutathione S-transferase(GST-P) positive foci and glutathione related enzyme system were investigated in carcinogen treated rats. Weaning male Sprague Dawley rats were divided into three groups and fed the diets of 15% corn(CO), perilla(PO), and sardine oil(SO), respectively. Hepatocellular carcinogenesis was initiated with diethylnitrosamine(DEN) and then fed the diet containing 0.02% 2-acetylaminofluorene(2-AAF) followed by 0.05% phenobarbital for 10 weeks. The hepatic tissues were homogenized and centrifugated to prepare microsomal and cytosolic fractions. The enzyme activities of hepatic glutathione S-transferase(GST), glutathione reductase(GR), and glutathione peroxidase(GPx) were determined from cytosolic fractions. The number of GST-P hyperplastic nodules was the highest in corn oil group at 6th week, the early stage of hyperplastic nodule formation. GST activities were increased significantly by carcinogens in all dietary groups after 6th wk. GR activities followed the same trend as GST activities. GPx activities were decreased by carcinogens in all dietary groups at 10th week. In this experiment, corn oil diet may have promotive effect on hyperplastic nodule formation during the early promotional stages of chemical carcinogenesis.

• The Korea Genome Conference
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• 2004.07a
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• pp.35.1-35.1
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• 2004

• Journal of Nutrition and Health
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• v.30 no.7
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• pp.803-812
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• 1997

The influences of dietary supplements of vitamin E on hepatocellular chemical carcinogenesis have been studied, Placental glutathione S-transferase(GST-P) positive foci area, antioxidant enzymes(superoxide dismutase(SOD), catalase, glutathione reductase, glutathione peroxidase, glutathione S-transferase(GST)), glucose 6-phosphatase(G6Pase) activities, and lipid peroxidation of mecrosomes(thiobarbituric acid reactive substances(TBARS) contents) were investigated. For is purpose , we used the murine chemical hepatocardinogenic procedure induced by modified Ito model, which consists of 200mg/kg body weight diethylinitrosamine (DEN) injection, 0.01% 2-acethlaminoflurene(2-AAF) feeding for 6 weeks, and partial hepatectomy on week 3. Weanling Sprague-Dawley male rats were fed pulverized Purina rat chow with 15, 000IU/kg diet vitamin E from initiation or promotion stages. We found that vitamin E supplement decreased the area of GST-P positive foci. Catalase, glutathione peroxidase, glutathione reductase. GST activities, and TBARS contents were decreased. On the other hand G6Pase activities were increased by vitamin E supplement. It seemed that vitamin E supplements helped endogenous defense systems against carcinogenesis by decreasing TBARS contents, $H_2O$$_2$ and organic peroxides. So, vitamin E seemed to protect cell from free radical damage in carcinogenesis. Anticarcinogenic effects of vitamin E were more effective at intiation that at promotion stage. These results suggest that vitamin E has suppressive effects on hepatocellular chemical carcinogenesis, probably through antioxidant effects against TBARS contents $H_2O$$_2$ and orgainc peroxides.

• Applied Microscopy
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• v.39 no.4
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• pp.283-289
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• 2009

In order to examine the effect of Injinhotang extract on the liver cancer induced by N-nitrosodiethylamine (NDEA) and carbon tetrachloride ($CCl_4$) in Rats. The animals were divided into three groups. The normal (Nor) group were fed basal diet. Control (Con) group were administered with NDEA (200 mg/kgb.w., i.p.) and $CCl_4$. Injinhotang extract (IJH) group treated with Injinhotang extract (260 mg/kg/day) for 8 weeks after NDEA+$CCl_4$. Enzymic antioxidants, such as superoxide dismutase (SOD) and catalase levels were determined in all the groups of animals. The activities of SOD were significantly increased in the Con, but the activities of catalase were decreased in the Con, but the anti-oxidative enzyme activities of superoxide dismutase and catalase were increased in the IJH. In the immunohistochemistry observation, treatment of Injinhotang extract reduced the rates of p53 immunoreactivity. According to the electron microscopical observation, in the liver cancer cells were increased the smooth endoplasmic reticulum and dilated the rough endoplasmic reticulum in the Con compared with IJH. These results suggest that administration of Injinhotang extract suppress or retard NDEA and $CCl_4$-induced liver cancer.

• Toxicological Research
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• v.13 no.1_2
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• pp.23-27
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• 1997

This study was performed to examine the anti-cancer effect of Red Ginseng in the DENGalN-PH-induced hepatic tumor model system in rats. One hundred of male SPF Sprague-Dawley rats(6weeks old) were randomly divided into five groups. Rats in groups 1, 2, 3, and 4 were administered to diethylnitrosamine intraperitoneally 200 mg/kg body weight for the caner initiation. Rats in group 5 were given to saline as a control. On two weeks after cancer initiation, rats in groups 1 and 3 were fed on diet containing 0.01% of acethylaminofiuorene(AAF) which is strong cancer-promotor for 6 weeks, while rats in groups 2 and 4 were fed on water containing 0.05% of phenobarbital which is weak cancer.promotor for 6 weeks. Rats in groups 1 and 2 were treated with diet containing 3% of Red Ginseng for six weeks(from 9th week till 15th week after cancer initiation). Rats in all groups were necropsied time-sequencially at 8, 15, and 36 weeks. The hepatic lesions of rat treated with carcinogens expressed glutathione S-transferase placental form(GST-P) at 8 week. The GST-P positive foci of rats treated with AAF were larger than that of any other rats, while the GST-P positive foci of rats treated with AAF and red ginseng were significantly decreased. This anti-cancer effect of Red ginseng might be involved in the enhacement of natural killer cell activity. To know whether there is direct relationship between Red Ginseng and natural killer cell activity, the activity of natural killer cell was examined after treatment AAF, AAF+Red ginseng and Red ginseng only, respectively. Comparing with natural killer cell activity in AAF-treated group, natural killer cell activity was significantly activated in AAF+ Red ginseng-treated group. This indicated that Red ginseng might enhance natural killer activity after treatment carcinogen in rats. These results suggested that Red ginseng might have a cancer prevention ability by promoting natural killer cell activity during hepatocarclnogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3959-3963
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• 2014

The tumour suppressor genes, p53 and pRb, are known to play important roles in neoplastic transformation. While molecular routes to the uncontrolled growth of hepatocytes, leading to primary liver cancer have generated considerable interest, the roles of p53 and pRb mutations in hepatocellular carcinoma (HCC) and hepatoblastoma (HB) remain to be clarified. We examined the immunohistochemical expression of p53 and pRb gene products in 26 HCC and 9 HB, sampled into tissue microarray blocks. 10 (38%) of 26 HCC showed > 10% tumour nuclear staining for p53 protein, 3 of these also being HbsAg positive. Conversely, none of 9 HB expressed nuclear p53 immunopositivity. Some 24 (92%) HCC and 8 (89%) HB showed loss of pRb nuclear expression. Two of the 26 HCC and one of the 9 HB showed >10% tumour nuclear staining for pRb protein. Our results suggest that p53 does not have an important role in the development of HB but may contribute in HCC. There is also loss of pRb expression in the majority of HCC and HB, supporting loss of pRb gene function in the hepatocarcinogenesis pathway. However, a comparison of the staining profiles of p53 and pRb proteins in HCC and HB did not reveal a consistent pattern to differentiate between the two types of tumours immunohistochemically. Hence the use of p53 and pRB protein expression has no contribution in the situation where there is a diagnostic difficulty in deciding between HCC and HB.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7139-7142
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• 2015

Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer related death overall. The role of insulin resistance in the development of HCC associated with chronic HCV infection has not been established. Resistin is a polypeptide hormone belonging to the adipokine family which could contribute to tumorigenesis and angiogenesis. Our aim was to study serum resistin and insulin resistance as risk factors for HCC in HCV cirrhotic patients. Materials and Methods: This prospective case controlled study included 100 patients with HCV related liver cirrhosis and HCC, 100 patients with HCV related liver cirrhosis without HCC and 50 apparently healthy participants as controls. For all subjects, liver profile, serologic markers for viral hepatitis, lipid profile, alpha-fetoprotein level (AFP), homeostasis model assessment (HOMA) were examined along with resistin. Results: HCC patients had higher mean values of HOMA-IR and resistin than cirrhotic patients and the control subjects (p<0.01). HOMA and resistin were considered independent risk factors in development of HCC, those patients with resistin > 12 ng/ml and HOMA > 4 being 1.6 times more likely to have HCC. Conclusions: HOMA and serum resistin allow for early identification of patients with cirrhosiswho are at substantially increased risk of HCC. Recommendation: HOMA and serum resistin could represent novel markers to identify HCV cirrhotic patients at greater risk of development of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2429-2434
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• 2016

Transforming growth factor-B1 ($TGF-{\beta}1$ )and its coreceptor endoglin (ENG) have been shown to contribute to hepatocellular tumor development and malignant progression. Our aim was to evaluate the serum expression levels of $ENG/TGF-{\beta}1$ mRNAs and risk of hepatocellular carcinoma in cirrhotic Egyptian patients. Our study included 77 subjects. Real time polymerase chain reaction was used to evaluate the expression level of ENG and $TGF-{\beta}1$mRNAs. The relative expression ratio of ENG mRNA was 0.82 (0.1 -3.2), 0.66 (0.15-5.3), 0.38(0.007-2.8) and 0.12 (0.00-0.22) and the relative expression ratio of $TGF-{\beta}1$mRNA was 1.4 (0.19 -6.2), 1.2 (0.22-4.3), 1.0 (0.15-4.4) and 0.6 (0.00-2.2) for cirrhotic HCC cirrhotic, HCC only and healthy control groups respectively. Increased ENG and $TGF-{\beta}1$ mRNA gene expression was correlated with TNM clinical stage. The expression ratio in TNM stage III-IV 1.1 (0.07-3.2), 1.55 (0.15-6.2) was statistically significantly higher than that in stage I-II 0.47 (0.007-2.8), 1.0 (0.31-4.4) (P<0.05). Our data suggested that increased ENG and $TGF-{\beta}1$ gene expression may participate in hepatocarcinogenesis and increased risk of HCC in individuals with cirrhosis. Early screening for evidence of cirrhosis and consideration of ENG and $TGF-{\beta}1$ as targets for therapy and treatment strategies are warranted.