• Toxicological Research
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• v.17
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• pp.41-45
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• 2001

The methods used for risk assessment from exposure to chemicals are well established. in most cases where toxicity other than carcinogenesis is being considered, the standard method relies on establishing the No Observed Adverse Effect Level (NOAEL) in the most sensitive animal toxicity study and using an appropriate safety factor (SF) to determine the exposure which would be associated with an acceptable risk. For carcinogens a different approach is used because it has been argued there is no threshold of effect. Thus mathematical equations are used to extrapolate from the high doses used in ani-mal experiments. These methods have been strongly criticised in recent years on several grounds. The most cogent criticisms are a) the equations are not based on a thorough understanding of the mechanisms of carcinogenesis and b) the outcome of a risk assessment based on such models varies more as a consequence of changes to the assumptions and equation used than it does from the data derived from carcinogenicity experiments. Other criticisms include the absence of any measure of the variance on the risk assessment and the selection of default values that are very conservative. Recent advances in the application of risk assessment emphasise that measures of both the exposure and the hazard should be considered as a distribution of values. The outcome of such a risk assessment provides an estimate of the distribution of the risks.

• Toxicological Research
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• v.17
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• pp.79-82
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• 2001

The infection of liver flukes, Clonorchis sinensis (CS) and Opisthorchis viverrini (OV), has been known as a risk factor to induce cholangiocellular carcinoma (CCC) in human living in the endemic area, providing promoting effect on the liver initiated by chemical carcinogens. The present study evaluated the relationship between the dosage level of dimethylnitrosamine (DMN) and the infection load of CS in the neoplastic development by histopathological examination of the treated hamsters. To evaluate the effects of DMN, different doses of DMN ranging from 0 to 25 ppm were administered to hamsters with 20 CS metacercariea. For the risk assessment of the infection load, 0, 5, 15, 50 CS metacercariae were respectively infected with 12 ppm DMN. The mortality was closely related to the infection load rather than the concentration of DMN. The infection of CS clearly promoted the induction of CCC even at dose level of 6 ppm DMN. Only five metacercariae were enough to promote CCC induction at the concentration of 12 ppm DMN.

• Analytical Science and Technology
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• v.7 no.2
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• pp.165-171
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• 1994

The effect of the chemical carcinogen dimetylnitrosamine(DMN) on the composition of amino acids of the liver in hamsters orally administered with DMN was studied by using the reversed phase high performance liquid chromatography technique. In the liver, the concentration of aspartic acid, glycine, glutamine, histidine, proline, tyrosine and leucine were increased ca. 2-fold of those observed in liver of control group, valine and tryptophan were increased ca. 3-fold, phenylalanine was markedly increased ca. 10-fold, whereas the concentration of threonine was decreased, serine, alanine, arginine, methionine, isoleucine and lysine were unchanged, respectively.

• 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.

• Korean Journal of Veterinary Research
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• v.26 no.1
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• pp.109-115
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• 1986

Experiments were performed on mice to investigate the effects of a polycyclic aromatic hydrocarbon, 3-methylcholanthrene (MCA) on Arthus reaction, delayed-type hypersensitivity (DTH) and antibody production to sheep red blood cells (SRBC). Mice were sensitized iv with 0.1ml of 1% SRBC suspension were treated with a single ip injection of olive oil alone or with different doses of MCA in oil (0.5~50mg/Kg) at various time before (-) or after (+) sensitization (day 0) and were challenged at 4 days after SRBC. Arthus reaction was measured at 3 hours after challenge and other responses at 24 hours. Treatment with MCA inhibited Arthus reaction and DTH to SRBC, measured by footpad swelling reaction, and this immunosuppressing effect was dependent on the dose and time of MCA treatment in relation to SRBC sensitization. Humoral immune responses as measured by serum hemagglutinin-and hemolysin-titers to SRBC were significantly depressed when MCA was injected before or at the same time of sensitization. However, the response was slightly depressed when injected after SRBC. These results indicate that MCA suppress the function of the cells involved in immune responses.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.3
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• pp.535-539
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• 2001

The modulating effect of feeding sea mustard (Undarina pinnatifida), a fiber-rich seaweed, during initiation and post-initiation phases of colon carcinogenesis was investigated in Sprague Dawley rats. Four groups of animals were exposed to the two weekly injections of a chemical carcinogen, azoxymethane (AOM). Animals were placed on diet containing 15% sea mustard during initiation. post-initiation or initiation+post-initiation phase of carcinogenesis for 10 weeks, and colonic aberrant crypt formation and cell proliferation were compared to those of rats fed semi-synthetic control diet. Results showed that sea mustard feeding significantly reduced the numbers of both aberrant crypts and aberrant crypt foci. Also, labeling indices and proliferation zones were significantly reduced in the colon of the rats fed sea mustard diets. These results indicate that the diet containing sea mustard may decrease the risk of colon cancer development, and a part of such effect may be mediated through both the blocking of initiation and the suppression of cell proliferation in the colonic crypts, although precise mechanisms should be further examined.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6669-6672
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• 2013

Colon cancer (CRC) is a serious health problem throughout the world. Development of novel drugs without side effects for this cancer is crucial. Luteolin (LUT), a bioflavonoid, has many beneficial effects such as antioxidant, anti-inflammatory and anti-proliferative potential. was a potent chemical carcinogen used for the induction of colon cancer. Colon carcinogenesis was initiated by intraperitoneal injection of azoxymethane (AOM) to mice at the dose of 15 mg/body kg weight in Balb/C mice for 3 weeks. Mice were treated with LUT at the dose of 1.2 mg/body kg weight orally. Mitochondrial enzymes such as isocitrate dehydrogenase (ICDH), ${\alpha}$-keto dehydrogenase (${\alpha}$-KDH), succinate dehydrogenase (SDH) and the activities of respiratory chain enzymes NADH dehydrogenase and cytochrome c oxidase were found to be elevated in AOM-treated animals. Treatment with LUT decreased the activities of all the parameters significantly. Hence, LUT might be a potent anticancer agent against colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5801-5805
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• 2015

As a cytosolic transcription factor, the aryl hydrocarbon (Ah) receptor is involved in several pathophysiological events leading to immunosuppression and cancer; hence antagonists of the Ah receptor may possess chemoprevention properties. It is known to modulate carcinogen-metabolising enzymes, for instance the CYP1 family of cytochromes P450 and quinone reductase, both important in the biotransformation of many chemical carcinogens via regulating phase I and phase II enzyme systems. Utilising chemically-activated luciferase expression (CALUX) assay it was revealed that intact glucosinolates, glucoraphanin and glucoerucin, isolated from Brassica oleracea L. var. acephala sabellica and Eruca sativa ripe seeds, respectively, are such antagonists. Both glucosinolates were poor ligands for the Ah receptor; however, they effectively antagonised activation of the receptor by the avid ligand benzo[a]pyrene. Indeed, intact glucosinolate glucoraphanin was a more potent antagonist to the receptor than glucoerucin. It can be concluded that both glucosinolates effectively act as antagonists for the Ah receptor, and this may contribute to their established chemoprevention potency.

• Journal of Nutrition and Health
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• v.27 no.6
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• pp.552-562
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• 1994

The study was designed to observe the effect of different dietary fats on the incidence of colorectal tumor and in vivo cell proliferation in colon carcinogenesis. Male Sprague Dawley rats were intrarectally infused with chemical carcinogen(methylnitrosourea, MNU) and fed 16%(w/w) fat diet containing one of dietary fats(beef tallow, corn oil, perilla oil) for 30 weeks. To measure in vivo cell proliferation, the incorporation of 5-bromo-2-deoxyuridine(BrdU) into DNA was localized using the monoclonal anti-BrdU antibody. Large number of tumors were found in the distal colon and tumor incidence was increased in the order of perilla oil(57.7%)$\alpha$-linolenic acid rich in perilla oil could have a protective effect against colon cancer compared to saturated fatty acid or n-6 linoleic acid.

• Journal of Environmental Health Sciences
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• v.31 no.4 s.85
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• pp.254-259
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• 2005

Permethrin, a synthetic pyrethroid insecticide, has been widely used to protect domestic animals and the public health, as well as in agriculture against a variety of pests, which provides potential for environmental exposure. Permethrin is classified as possible human carcinogen and endocrine disrupting chemical by many international authorities. However, its developmental effects have been rarely studied. This study investigated the effects of permethrin during embryo-genesis. Developmental toxicity of permethrin was evaluated using short-term in vitro battery system. Gestation day 9.5 rat embryos (organogenesis) were cultured with permethrin (0.1,0.4 and 0.8 mg/ml) for 48 hours using whole embryo culture system. All the treatments exhibited significant decreases in the total morphological score. Permethrin induced significant growth retardation and the developmental abnormality at doses of 0.4 and 0.8 mg/ml. Moreover, the DNA and protein contents of embryos decreased in dose-dependent manner. These observations suggest that permethrin contributes to toxicity on embryonic developments in rats.