• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2825-2830
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• 2014

Purpose: To study the effect of Cleistocalyx nervosum extract (CE) on diethylnitrosamine (DEN) and phenobarbital (PB) induced oxidative stress in early stages of rat hepatocarcinogenesis. Materials and Methods: Male Wistar rats were divided into 4 groups, with Group 1 as a negative control and Group 2 was a positive control receiving DEN injections once a week and PB in drinking water for 6 weeks. Two weeks before DEN initiation and PB treatment, Groups 3 and 4, were fed with 500 and 1000 mg/kg of CEs, respectively, for 8 weeks. Results: A number of GST-P-positive foci, preneoplastic lesions, in the liver were markedly increased in carcinogen administered rats, but was comparatively decreased in rats treated with 1000 mg/kg of CE. The CE reduced malondialdehyde in serum and in the livers of rats treated with DEN and PB. Moreover, CE significantly increased the activities of glutathione peroxidase and catalase in rat liver. Conclusions: CE appeared to exert its chemopreventive effects by modulating antioxidant status during DEN and PB induced early stages of hepatocarcinogenesis in rats.

• Toxicological Research
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• v.34 no.4
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• pp.291-296
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• 2018

Chemical carcinogenesis is a multistep process. Genotoxic carcinogens, which are DNA-reactive, induce DNA adduct formation and genetic alterations in target cells, thereby generating mutated cells (initiation). Subsequently, preneoplastic lesions appear through clonal proliferation of the mutated cells and transform into tumors (promotion and progression). Many factors may influence these processes in a dose-dependent manner. Therefore, quantitative analysis plays an important role in studies on the carcinogenic threshold of genotoxic carcinogens. Herein, we present data on the relationship between key carcinogenic events and their deriving point of departure (PoD). Their PoDs were also compared to those of the carcinogenesis pathway. In an experiment, the liver of rats exposed to 2-amino-3,8-dimethylimidazo-(4,5-f)quinoxaline (MeIQx) was examined to determine the formation of MeIQx-DNA adducts, generation of mutations at LacI transgene, and induction of preneoplastic glutathione S-transferase placental form (GST-P)-positive foci and tumors (benign and malignant). The PoDs of the above key events in the carcinogenicity of MeIQx were increased as the carcinogenesis advanced; however, these PoDs were lower than those of tumor induction. Thus, the order of key events during tumor induction in the liver was as follows: formation of DNA adducts ${\ll}$ Mutations ${\ll}$ GST-positive foci (preneoplasia) ${\ll}$ Tumor (adenoma and carcinoma). We also obtained similar data on the genotoxic and carcinogenic PoDs of other hepatocarcinogens, such as 2-amino-3,8-dimethylimidazo(4,5-f)quinoline. These results contribute to elucidating the existence of a genotoxic and carcinogenic threshold.

• Korean Journal of Veterinary Pathology
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• v.2 no.2
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• pp.95-106
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• 1998

The prevalence of primary liver carcinoma (PLC) is relatively high in Clonorchis sinensis (CS) endemic areas in Korea. PLC is a malignant tumor which can be subclassified into hepatocellular carcinoma and cholangiocarcinoma(CC). CC has been associated with clonorchiasis, but it is unclear whether clonorchiasis is associated with hepatocarcinogenesis. This experiment was designed to investigate relationships between clonorchiasis and early changes of hepatocarcinogenesis. Sixteen Sprague-Dawley rats weighing 150g were divided into two groups of 8 rats in each. All rats were fed choline-devoid(CD) diet for 4 weeks. Group 1 was given 0.015-0.020% diethylnitrosamine(DEN) as drinking water for 1 week. After one week, the rats were treated orally with 1% N-acetylaminofluorene(AAF) (5 times per week for 2 weeks). Group 2 was treated equally to group 1 except for CS infection during AAF treatment. Two rats in each group were sacrificed at 4th, 5th, 6th and 7th week of the experiment. Livers were stained with OV -6, proliferating cell nuclear antigen(PCNA) and GST-p. Results were as follows: Group 2 livers showed more oval cell proliferation in parenchyma and portal areas at the 4th, 5th, 6th and 7th weeks than did livers of group 1 (p＜0.01). PCNA was mostly localized in oval cell populations, rather than hepatocytes and biliary cells. The ratio of oval cells to hepatocytes was much higher in group 2 than in group l(p＜0.01 The ratio of hepatocytes to biliary cells is higher in group 2 than in group 1 (p＜0.05), More group 2 acidophilic foci reacted to GST-p monoclonal antibody than in the noninfected group. It appeared that CS infection promoted potentially precancerous acidophilic foci and oval cell proliferation.

• Culinary science and hospitality research
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• v.4
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• pp.129-146
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• 1998

The effects of vitamin E supplement on 15%(w/w diet) perilla or corn oils were studied in rat hepatocellular chemical carcinogenesis induced by modified Solt & Farber model, which consists of 20mg/kg body weight diethylintrosamine(DEN) injection, 3 weeks feeding of 0.02%2-acetylaminofluorene(2-AAF) and partial hepatectomy. The area of placental glutathione S-transferase(GST-P) positive foci tended to be smaller in perilla oil group had lower thiobarbituric acid reactive substances(TBARS) CONTENT. Fatty acid compositions in microsomal membrane were reflected by dietary fatty acid compositions, and not affected by carcinogen treatment or vitamin E supplement. By vitamin E supplement, linolenic acid contents of perilla oil group were much increased. By carcinogen treatment, membrane stability decreased significantly in corn oil, but maintained in perilla oil groups Vitamin E supplemental effect was noticed only in the corn-carcinogen group. Perilla oil may prevent hepatocarcinogenesis by maintaining membrane stability and by reducing cytochrome P-450 content. Vitamin E supplement did not seem to have the effect on hepatocarcinogenesis, but prevented lipid peroxidation, reduced cytochrome P-450 content and maintained membrane stability.

• Journal of Food Hygiene and Safety
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• v.16 no.3
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• pp.212-220
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• 2001

To investigate the modifying effect of Kwao Kreu, Pueraria mirifica (PM), we performed two kind of studies which are the non-surgical medium-term carcinogenicity study and the modulation of gap junctional intercellular communication study. The first study, a non-surgical medium-term carcinogenicity bioassay was done to investigate the modifying effect of Kwao Keru, Pueyaria mirifca (PH), a rejuvenating folk medicine from Thailand, on the male F344 rat liver. Specific pathogen free, male 6-week-old F3444 rats were divided into ten groups. To induce hepatocarcinogenesis, those in all groups were given a single i.p. injection of DEN (200 mg/kg) and were received two i.p. injection of DGA (300 mg/kg) at the ends of weeks 2 and 5. Rats of group 3-6 were given sodium phenobarbital (PB 0.05% in drink). A diet containing 10 mg/kg PM was given to group 2 during the post-initiation phase and to groups 4 and 5 during promotion and initiation phase, respectively. Group 6 was given the experimental diet alone throughout the experiment (8 weeks). Rats of group 7, 8, 9 and 10 were fed 1000 mg/kg PH in the same manner as group 2, 4, 5 and 6. All animals were sacrificed at 8 weeks after DEN administration. Result of the immunohistochemical staining of the glutathione S-transferase placental form (GST-p) indicated that the numbers and areas of the preneoplastic leisions were not significantly changed in all PM treatment group comparing to control group. Also the numbers and areas of GST-p positive foci among group 7, 8, 9 and 10 were not significantly changed in comparing to control group. To study the effect of PM on the modulation of gap junctional intercellular communication, the present study was performed scrape-loading dye transfer (SL/DT) assay in human keratinocytes. The results showed that PM could not modulate GJIC. These results indicate that Pueraria mirifica may have no carcinogenic effects on experimental hepatocarcinogenesis in rats and gap junctional intercellular communication in human keratinocyte.

• Journal of Environmental Health Sciences
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• v.32 no.1 s.88
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• pp.60-66
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• 2006

Bisphenol A(BPA) was known as an endocrine disrupting chemical. This study was conducted to assess the effect of BPA, weaker estrogen, on the preneoplastic and neoplastic lesions induced by diethylnitrosamine (DEN). One hundred male F344 rats were divided into four groups which were treated with DEN followed by BPA. To make liver tumor early, we conducted that DEN containing osmotic pump implanted into rat abdominal cavity. Then diet containing BPA were fed to the rats. All animals were sacrificed at 10 and 18 weeks. Body weights were significantly decreased in 4000ppm at 18 weeks. Relative Liver weights of 4000 ppm BPA treated group were significantly increased compared to that of DEN alone group at 18 weeks. There were no significant differences of liver tumor incidences. Sum area of GST-P positive foci and BrdU labeling indices of BPA treated group were not significantly different compared to those of control group. These results suggest that BPA have no effects in preneoplastic and neoplastic lesions on DEN-induced hepatocarcinogenesis.

• Korean Journal of Veterinary Pathology
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• v.1 no.1
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• pp.13-25
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• 1997

The anticarcinogenic effects of dimethyl disulfide(DMDS, methyl disulfide)and diallyl disulfide(DADA, allyl disulfide) were studied in a 28 weeks rat multi-organ carcinogenesis model. neoplastic and preneoplastic lesions were observed in the liver kidney thyroid gland esophagus duodenum colon, rectum and adrenal gland. Tesults showed that neoplastic lesions in the kidney liver and thyroid gland were inhibited by DADS but those in the liver and colon were enhanced by DMDS when compared to positive control group. incidence of neoplastic lesions in the other organs were not changed by DMDS or DADS exposure. While GST-p positive foci in the liver were increased by DMDS, DADS had no effect. There was no significant histopathological lesion in DMDS or DADS treated group without pretreatment with carcinogens.

• Korean Journal of Veterinary Pathology
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• v.1 no.2
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• pp.107-118
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• 1997

The anticarcinogenic effects of allyl methyl trisulfide(AMT) and methyl propyl disulfide(MPD) were studied in a 28 weeks rat multi-organ carcinogenesis model. Tumor incidence rate was decreased by AMT or MPD treatment comparing with the positive control. AMT treatment significantly decreased the incidence of neoplastic and preneoplastic lesions in the kidney thyroid gland urinary bladder alimentary tract lung and Zymbal's gland. MPD also inhibited incidence of noplastic and preneoplastic lesions in the liver kidney urinary bladder alimentary tract lung and Zymbal's gland but increased that in the thyroid gland. GST-p positive foci in the liver were slightly decreased by AMT or MPD. There was no significant histopathological lesions in AMT or MPD treated group without pretreatment of carcinogens.

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.277-287
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• 2002

The chemopreventive effects of ginseng on rat carcinogenesis models were investigated, In the present study, the inhibitory effects of white and red ginseng on tumor development were examined using medium-term liver, initiation and medium-term multi-organ carcinogenicity bioassay systems. No modifying potential of the ginsengs was evident in terms of the numbers or areas of glutathione S-transferase placental form (GST -P)-positive foci, which is a marker of preneoplastic lesion in rat livers. However, white ginseng, but not red ginseng was found to decrease the incidences of adenocarcinoma of the small intestine and colon in the medium-term multi-organ carcinogenesis model. These results indicate that white ginseng may have inhibitory effects on progression stage of rat intestinal carcinogenesis, but the influence is not strong. Ginseng is unlikely to have promoting or inhibitory effects in other organs under the present type of experimental conditions. Possible application on ginseng for chemoprevention of colon cancer in humans, can be concluded given the lack of obvious adverse effects.

• Journal of Food Hygiene and Safety
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• v.8 no.1
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• pp.37-53
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• 1993

F. moniliforme MRC 826, a common fungal contaminant of com, has been known to produce a group of mycotoxins, the fumonisins. By thin layer chromatography, fumonisin $B_{1}$ was detected in the F. moniliforme MRC 826 com culture material(CM) extracts. This study was performed to compare the toxicity and carcinogenicity of F. moniliforme MRC 826 CM with those of aflatoxin $B_1(AFB_1)$ in rats. The toxicity was tested over a period of 7 days in ten female Sprague-Dawley (SD) rats. Treatment group were fed a 1 : 1 mixture(wt/wt) of ground CM and basal diet in powder form, while other negative control group were given basal diet alone. The principal pathological changes in rats treated with 50% CM were hepatocellular hydropic degeneration and renal tubular necrosis. The cancer-promoting activity of CM was evaluated in the rat liver diethylnitrosamine-two thirds partial hepatectomy(DEN-PH) model for carcinogenesis. 70 male SO rats(ca. 170 g) were randomized into 5 groups. Group I served as the positive controls and received the basal diet containing 2 ppm $AFB_{1}$ group 2 received 5% CM, group 3 received 2.5% CM, group 4 received 5% normal com and group 5 received 2.5% normal com. 5% treated group showed cancer promoting activity in rat liver using DEN as initiator and the induction of glutathione S-transferase placental form positive foci as an end point after 6 weeks of promotion.