• Environmental Mutagens and Carcinogens
• /
• v.24 no.1
• /
• pp.25-32
• /
• 2004

To validate and to estimate the chemical hazard playa very important role to environment and human health. The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this resepct, the clastogenicity of 17 synthetic chemicals was evaluated with bone marrow micronucleus assay in mice. The positive control, mitomycin C (2 mg/kg, i.p.) revealed significant induction ratio of percentage of micronucleated polychromatic erythrocytes/1,000 polychromatic erythrocytes compared to solvent controls. The chemicals with relatively high $LD_{50}$ value such as allyl alcohol (CAS No. 107-18-6), 2,4-pentanedione (CAS No. 123-54-6) and 4-chloro-3,5-dimethylphenol (CAS No. 88-04-0) revealed no significant induction of micronucleated polychromatic erythrocytes in mice. From this results, 17 synthetic chemicals widely used in industry have revealed no significant micronucleus induction of clastogenicity in mice in this experiment.

• Environmental Mutagens and Carcinogens
• /
• v.21 no.1
• /
• pp.34-43
• /
• 2001

Di-2-ethylhexyl phthalate (DEHP) is the most commonly used phthalate ester in polyvinyl chloride formulations including food packing and storage of human blood. DEHP is a well known as non-genotoxic carcinogen and endocrine disrupting chemical (EDC). DEHP have shown all negative results in ICH-guildeline recommended standard genotoxicity test battery. In this study, to assess the clastogenic and DNA damaging effect in human-derived tissue specific cells, DEHP was treated in human derived MCE-7 cells, HepG2 cells, LNCap cells, BeWo cells, MCE-10A cells, and female peripheral blood cells using micronucleus assay and in human breast carcinoma MCF-7 cells up to $1.28$\times$10^{-2}$ M using Comet assay. The in vitro micronucleus assay is a mutagenicity test system for the detection of chemicals which induce the formation of small membrane bound DNA fragment i.e. micronuclei in the cytoplasm of interphase cells, originated from clastogenic and/or aneugenic mechanism. The single cell gel electrophoresis assay (Comet assay) is used to detect DNA strand-breaks and alkaline labile site. In our results, DEHP increased significantly and/or dose-depentently and time-dependently micronucleus frequency at the 6 and 24 hr without metabolic activation system only in MCE-7 cells. DEHP treated with 2 hrs in MCF-7 cells using Comet assay induced DNA damage dose-depentantly.

• Journal of Nutrition and Health
• /
• v.26 no.3
• /
• pp.313-324
• /
• 1993

Sister chromatid exchange(SCE) has recently become a common cytogenic assay system for detecting exposure to chemical mutagens and carcinogens. One application of SCE is the monitoring of populations believed to be exposed to such agents. A cross-sectional study of SCE frequency in peripheral blood lymphocytes from 40 college students aged 18 to 26 years was conducted. The effects of cigarette smoking alcohol and coffee consumption, dietary and environmental factors on SCE were assessed. A mean spontaneous SCE per cell for the smokers(4.88$\pm$0.17). The SCE levels of the smokers were associated with the personal smoking amount ; the observed increase in the SCE frequency correlated with the number of cigarettes smoked per day (P<0.05). There was no effect of age on SCE. There were positive linear relationship between SCE and food frequency score of meat and fish group (P<0.05) or instant food group(P<0.01) in non-smokers. But in smokers, a significant inverse association between SCE and food frequency score of green and yellow vegetable group(P<0.05). Alcohol intake produced a significant increase(P<0.01) of SCE in comparison with the mean SCE for those not drinking alcohol in combine subjects. Other dietary parameters, including coffee intake, use of artificial sweetners and processed foods, did not show any increase in SCE. SCEs were inversely related to blood glucose and serum cholesterol levels of the combine subjects. No significant correlations were found between SCE frequencise and any other hematological parameters of the subjects.

• Environmental Mutagens and Carcinogens
• /
• v.22 no.4
• /
• pp.324-330
• /
• 2002

Bisphenol A (BPA) is a monomer widely used in the manufacturing polycarbonate plastics or epoxy resin, and xenobiotics recently known as endocrine disrupting chemical. In this paper, to assess the effects of bisphenol A on immunopathological parameters (body weight, organ weight, hematological parameters, cellularity and surface marker) in mice, ICR female mice were orally exposed to BPA dissolved in olive oil as concentrations of 100, 500, 1000 ㎎/㎏/day b.w. 5 days a week for 30 days (subacute exposure). Liver - and kidney weight was significantly increased as dose-dependent manner, but body- , spleen- and thymus- weight didn't changed. In hematological parameters, WBC and MCHC were lowered but HCT and MCV were siginificantly enhanced. There was no significant differences in peritoneal macrophages number of the mice exposed to BPA. However, number of splenocytes of spleen, CD3/sup +/ and CD4/sup +/ cell in splenocytes, CD4/sup +/ and CD8/sup +/ cell in thymocytes were decreased at the mice subacutely exposed to BPA. In addition, BPA decreased expression of B7-1 and B7-2 on macrophages. Therefore, these results showed BPA may affect hematological parameters, cellularity and surface marker of immunocytes.

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

• Journal of Nutrition and Health
• /
• v.36 no.8
• /
• pp.851-858
• /
• 2003

Sister chromatid exchange (SCE) has recently become a common cytogenic assay system for detecting exposure to chemical mutagens and carcinogens. One application of SCE is the monitoring of populations believed to have been exposed to such agents. A cross-sectional study of SCE frequency in peripheral blood lymphocytes from 45 Koreans aged 61 to 84 years was conducted. The effect of cigarette smoking and age on SCE was assessed by different degrees of smoking status such as smokers (n = 14), ex-smokers (n = 16) and non-smokers (n = 15). Mean spontaneous SCE per cell for the smokers (11.5 $\pm$ 1.1) was significantly higher (p < 0.05) than that for the non-smokers (8.8 $\pm$ 0.3). However, mean SCE frequencies per cell for the ex-smokers (10.3 $\pm$ 0.6) were not significantly different from those of the smokers or the non-smokers. The smokers showed an increased number of high SCE frequency cells (HFCs) when compared to the ex-smokers and non-smokers (p < 0.05). The mean SCE frequencies of the non-smokers showed a statistically significant increase (p < 0.05) with the subject's age. These results show that age and smoking habits contribute a great deal in setting a higher degree of basal DNA damage in elderly Koreans, and smoking appeared to be a more significant damaging factor than age.

• Environmental Mutagens and Carcinogens
• /
• v.9 no.1
• /
• pp.13-22
• /
• 1989

The effect of novobiocin (NOV), and inhibitor of topoisomerase II, on ethyl methanesulfonate (EMS)-or bleomycin (BLM)-induced DNA repair synthesis was examined during the cell cycle of Chinese hamster ovary (CHO)-K1 cells. Three assays were employed in this study: cell survival, alkaline elution and unscheduled DNA synthesis. EMS was effective at killing CHO cells in G1 phase, wheras BLM preferentially killed cells in G2 and S phases. EMS induced the much more amount of DNA damage in G1 phase, while BLM induced in G2 phase than the other phases. The both of pre- and post-treatment with BOV inhibitied EMS- or BLM-induced DNA repair synthesis in G1 and G2 phases, and pretreatment with NOV inhibited more effectively than the post-treated group. These results suggested that CHO cells exhibited a differential sensitivity to cell lethality and DNA damage in relation to cell cycle according to used chemical agents, and that DNA topoisomerase II participated in an initial stage of DNA repair.

• Environmental Mutagens and Carcinogens
• /
• v.9 no.1
• /
• pp.23-32
• /
• 1989

Chinese hamster ovary (CHO)-K1 cells echibited a differential sensitivity in the process of DNA repair synthesis induced by ethyl methanesulfonate (EMS) or bleomycin (BLM) in relation to cell cycle. Two assays were employed in this study: alkaline elution and unscheduled DNA synthesis. The post-treat-ment with aphidicolin (APC), an inhibitor of DNA polymerase alpha, inhibited DNA repair synthesis induced by EMS in G2 phase, while APC did not show any effect on BLM-induced DNA repair synthesis in all phases. On the other hands, the 2', 3'-dideoxythymidine (ddTTP), an inhibitor of DNA polymerase beta, inhibited DNA repair synthesis induced by EMS or BLM in both of G1 and G2 phases. These results suggested that the involvement of DNA polymerase alpha and beta in DNA repair was dependent on cell stage or used chemical agent.

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

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.5449-5454
• /
• 2013

Background: A large variety of familiar and non-familiar lung carcinomas (LC) are caused by long term exposure to chemical carcinogens that are present in tobacco smoke. We aimed to investigate the prevalence of 5 thrombophilic germ-line mutations in patients with lung carcinomas. Materials and Methods:A total of 52 LC patients and 212 healthy controls from same population were analyzed for FV Leiden, factor V H1299R (R2), PAI-1, MTHFR C677T, MTHFR A1298C, ACE I/D, and Apo E genes and compared. Results: Overall, heterozygous and/or homozygous point mutations in FV Leiden Apo E2, PAI-1 and MTHFR C677T genes were associated with LC in the current cohort. There was no meaningful association between LC and ACE I/D gene markers. Conclusions: The current results showed that LC is related to combined thrombophilic gene mutations and individuals with homozygosity of 4G in PAI-1 and MTHFR C677T genes and heterozygosity of FV Leiden, Apo E4 genes have a germ-line risk for LC tumorigenesis.