• 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.

• Archives of Pharmacal Research
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• v.21 no.4
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• pp.363-369
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• 1998

Glutathione S-transferase placental form (GST-P) positive foci development and its expression in liver exposed by nongenotoxic carcinogens phenobarbital (PB) and clofibrate (CF), and genotoxic carcinogen 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) were investigated as a measure of carcinogenic potential of these chemicals. Male F344 rats were initially given a single intraperitioneal injection of diethyinitrosamine (200 mg/kg), and 2 weeks later, animals were fed diets containing 0.03% IQ or 0.5% CF or 0.05% PB or basal diet as a control for 6 weeks. All rats were subjected to two-thirds partial hepatectomy (PH) at week 3. Sequential sacrifice of rats was performed at 8 weeks or 52 weeks, and liver tissues were examined for immunohistochemical staining of GST-P positive foci. The numbers (No./$cm^2$) and areas ($mm^2$/ $cm^2$) of GST-P positive foci were increased by IQ or PB, but were decreased by CF compare to the control. Consistent with the development of GST-P positive foci, a time-related increase in the expression of GST-P mRNA was found in the rats treated with IQ, whereas CF decreased it. The incidence of hepatocellular carcinoma at 52 weeks was increased by all three chemicals. These results show that PB and IQ induced GST-P positive foci, but the peroxisome proliferator CF did not, which suggest that the prediction of carcinogenic potency based on the development of prenoplastic foci may cause false negative in a particular category compounds like peroxisome proliferators.

• Korean Journal of Veterinary Research
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• v.28 no.2
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• pp.227-239
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• 1988

In order to investigate the morphological characteristics of dendritic cells in the mammary gland, the appearance on the clear cells(CLs) or ATPase-positive dendritic cells(APDCs) have been observed by the light microscope. The results obtained were summarized as follows: CLs were observed in the mammary tissues of the experimental animals, such as mice, rats, guinea pigs, rabbits, cats, dogs, pigs, cows and Korean native goats, and these CLs were confirmed as the ATPase-positive cells of typical dendritic appearance(APDCs), The APDCs were distributed in between the secretory epithelial cells, between the secretory epithelial cells and the myoepithelial cells, the basal area of the secretory epithelial cells, the interalveolar and interlobular connective tissues, and in between the epithelial cells of secretory duct. The APDCs were observed more frequently during the middle period of lactation than the other periods, and were irregularly or uniformly distributed according to the location. During the middle period of lactation, there were notable quantitative differences in the APDSs depending on the mammary glands of mice, rats, guinea pigs, rabbits and cats, The most prominent differences were recognized among the mice, guinea pigs and cats. The number of AP DCs per unit area was statistically fewer in the guinea pigs($209.07{\pm}51.75cells/mm^2$) than in the mice($221.00{\pm}50.94cells/mm^2$) and cats($223.56{\pm}49.68cells/mm^2$) (respectively, p<0.05, p<0.05). Among the A/J, DBA/2, C57BL/6 and NIH(GP) mice, the mean densities of APDCs was statistically significantly fewer in the DBA/2($196.65{\pm}43.47cells/mm^2$) than in the C57BL/6($248.40{\pm}41.40cells/mm^2$) and NIH(GP) ($235.98{\pm}55.89cells/mm^2$) (respectively, p<0.0000, p<0.0000), however no significant difference between the C57BL/6 and the NIH(GP) was recognized (p>0.1). Among the F344, SD and W rats, the statistical analysis were confirmed that there were significantly fewer APDCs in the F344($198.72{\pm}47.61cells/mm^2$) than in the SD($227.70{\pm}41.40cells/mm^2$) and W($223.56{\pm}49.68cells/mm^2$) (respectively, p<0.0000, p<0.0001), however no significant difference between the SD and the W was recognized(p>0.1). The mean difference between the inbred and the noninbred counts in the mice was statistically significant (p<0.0001), and the similar result was presented in the rats(p<0.0000).

• Korean Journal of Pharmacognosy
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• v.46 no.1
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• pp.44-51
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• 2015

The objective of this study is to characterize a toxicity of Polygalae Radix (PR) in F344 rats and to find a dose levels for the 13 weeks toxicity study. PR is well known as medicinal herb in many Asian countries for treatment of expectorant, tonic, tranquillizer, antipsychotic agent and functional diet for improving memory. However, there is insufficient background information on toxicological evaluation of PR extract to support its safe use. Therefore, we conducted toxicological evaluation of this drug in compliance with OECD and KFDA guideline in this study. The extract of PR was administered orally to F344 rats at dose levels of 0, 500, 1000, 2000, 3500 and 5000 mg/kg/day for 2 weeks. Each group was composed to five male and five female rats. In the result, there were no treatment PR-related adverse changes in food consumption, hematology, clinical chemistry, urinalysis, gross finding at necropsy, organ weight examination. Four males at 5000 mg/kg/day were found dead during the treatment period. These animals showed salivation. The cause of death is still under investigation. The animals treated at 500, 1000, 2000, 3500 and 5000 mg/kg/day showed salivation and all animals at 5000 mg/kg/day exhibited lower body weight and cumulative weight gain in compared to those of control animals. Therefore, we recommend that a dose group of 3500 mg/kg/day is a highest treatment group in 13-week exposure study.

• Journal of the Korea Institute of Military Science and Technology
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• v.14 no.6
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• pp.1159-1165
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• 2011

Telemetry techniques of rats have been used for assessing safety pharmacology of drugs and chemicals. Biological signals including blood pressure and heart rate measured under anesthesia were significantly different from those obtained under normal conditions. The stress of restraint in awake animals can also affect the accuracy of physiological evaluation. This paper details the surgery required to allow key cardiovascular parameters to be determined. The telemetric measurement of cardiovascular parameters such as blood pressure, heart rate, electrocardiograph(ECG) established. We carried out the continuous monitoring of cardiovascular parameters using the telemetry system in F344 rats. During the measurement, no significant changes were observed in the heart rate and blood pressure. ECG signals and body temperature were also constant during the measurement of biological signals. With the results of this study, we conclude that this telemetry system can be applied usefully for the assesment of biological parameters in the rats.

• Toxicological Research
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• v.20 no.3
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• pp.273-280
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• 2004

The present study was carried out to investigate the potential toxicity of dimethyl disulfide by a 2-week inhalation in F344 rats. The test article, dimethyl disulfide, was exposed by inhalation to male and female rats at dose levels of 0, 33, 100, or 300 ppm/6 hrs/day for 2 weeks. At the end of treatment period, all males and females were sacrificed. During the test period, clinical signs, mortality, body weights, food consumption, hematology, serum biochemistry, and gross findings were examined. The mean body weights of the male 300 ppm group and the female 33 ppm or higher dose groups were significantly lower than those of the control group, respectively. The mean food consumption at male 300 ppm and female 100 and 300 ppm were significantly decreased compared with the controls. Some treatment-related serum biochemical changes, including decreased alkaline phosphatase at male 300 ppm and female 100 and 300 ppm, reduced total bilirubin at male 300 ppm, and decreased alanine aminotransferase at female 300 ppm, were observed in a dose-dependent manner, but these findings were considered to be of no toxicological significance. There were no adverse effects on mortality, clinical signs, hematology, and necropsy findings in any treatment group. Based on these results, it was concluded that the 2-week repeated dose of dimethyl disulfide by inhalation resulted in suppressed body weight gain and decreased food consumption at the dose of male 300 ppm and suppressed or reduced body weight gain and decreased food consumption at the dose of female 33 ppm or higher. In the present experimental conditions, the no-observed-adverse-effect level (NOAEL) was considered to be 100 ppm/6 hrs/day for male rats and below 33 ppm/6 hrs/day for female rats.

• Korean Journal of Pharmacognosy
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• v.34 no.3 s.134
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• pp.218-222
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• 2003

The mistletoe lectins are major active components in the extrct of Viscum album var. coloratum. This study was performed to investigate the anti- skin cancer effect of Korean mistletoe extract intensified with mistletoe lectin (KI 2103S). B16F10 melanoma cells were allografted in C57BL/6 mice and F344 rats. The effect of KI 2103S on melanoma was measured by monitoring tumor index. The KI 2103S was injected intra-tumorally and tumor index was decreased in dose dependent manner.

• 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.

• 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.

• Food Science and Biotechnology
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• v.16 no.6
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• pp.1064-1068
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• 2007

We evaluated the effect of soybean dongchunghacho [SD, cultivated dongchunghacho fungus (Paecilomyces tenuipes) on soybeans] on dimethylhydrazine (DMH)-induced DNA damage and oxidative stress in male F344 rats. The animals were divided into 3 groups and fed a casein-based high-fat, low fiber diet without (DMH group) or with 13%(w/w) of soybean (DMH+S group), or SD (DMH+SD group). One week after beginning the diets, rats were treated weekly with DMH (30 mg/kg, s.c.) for 6 weeks; dietary treatments were continued for the entire experiment and endpoints measured at 9 weeks after the first DMH injection. SD supplementation reduced DMH-induced DNA damage in colon cells and reduced plasma lipid peroxidation. Thus, SD may have therapeutic potential for early-stage colon carcinogenesis.