• Toxicological Research
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• v.22 no.4
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• pp.423-429
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• 2006

Recent reports on the photocarcinogenicity and photogerotoxicity of many compounds led to an increasing awareness for the need of a standard approach to test for photogenotoxicity. The comet assay has been recently validated as a sensitive and specific test system for the quantification of DNA damage. Thus, the objectives of this study are to investigate the utility of photo-comet assay for detecting photo-mutagens, and to evaluate its ability to predict rodent photo-carcinogenicity. Photo-comet assays were performed using L5178Y $Tk^{+/-}$ mouse lymphoma cells on five test substances (8-methoxypsoralen, chlorpromazine, lomefloxacin, anthracene and retinoic acid) that demonstrated positive results in photocarcinogenicity tests. For the best discrimination between the test substance-mediated DNA damage and the undesirable DNA damage caused by direct UV absorption, a UV dose-response of the cells in the absence of the test substances was firstly fnalized. Out of 5 test substances, positive comet results were obtained for chlorpromazine, lomefloxacin, anthracene and retinoic acid while 8-methoxypsoralen found negative. An investigation into the predictive value of this photo-comet assay for determining the photocarcinogenicity showed that photo-comet assay has relatively high sensitivity. Therefore, the photo-comet assay with mammalian cells seems to be a good and sensitive predictor of the photocarcinogenic potential of new substances.

• Archives of Pharmacal Research
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• v.23 no.2
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• pp.139-146
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• 2000

7- Bromomethylbenz[a]anthracene is a known mutagen and carcinogen. The two major DNA adducts produced by this carcinogen, i.e., $N^2$-(benz[a]anthracen-7-yl methyl)-2'-deoxyguanosine (2, b[a]$a^2$G) and $N^6$-(benz[a]anthracen-7-ylmethyl)-2'-deoxyadenosine (4, b[a]$a^6$/A), as wel 1 as the simpler benzylated analogs,$N^2$-benzyl-2'deoxyguanosine (1, $bn^2$G) and $N^6$-benzyl-2'-deoxyadenosine (3, $bn^6$/A), were prepared by direct aralkylation of 2'-deoxyguanosine and 2'-deoxyadenosine. To determine the site-specific mutagenicity of these bulky exocyclic amino-substituted adducts, the suitably protected nucleosides were incorporated into 16-base oligodeoxyribonucleotides in place of a normal guanine or adenine residues which respectively are part of the ATG initiation codon for the lac Z' \alpha-complementation gene by using an in situ activation approach and automated phosphite triester synthetic methods. The base composition and the incorporation of the bulky adducts into synthetic oligonucleotides were characterized after purification of the modified oligonucleotides by enzymatic digestion and HPLC analysis.

• Toxicological Research
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• v.30 no.3
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• pp.179-184
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• 2014

Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems.

• Korean Journal of Food Science and Technology
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• v.27 no.6
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• pp.944-949
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• 1995

To investigate the effect of processing on the antimutagenicity of rice, antimutagenic effect of rice products including cooked rice, plain steamed rice bread(baikseolgi) and parched rice powder were observed. They showed inhibitory effects of $46%{\sim}100%$ on the frameshift mutation, whereas they showed little inhibitory effect on the base substitution mutation in the Salmonella typhimurium reversion assay. No inhibitory effect was found in the SOS chromotest. Inhibitory effect was more clearly observed on the indirect-acting mutagen than on the direct-acting mutagen. In case of the S. typhimurium reversion assay, the range of inhibition rate against the frameshift and base substitution mutation was $75%{\sim}100%$ and $66%{\sim}87%$, respectively, and was $19%{\sim}67%$ in the SOS chromotest. Antimutagenic activity of raw rice was supposed to be maintained in processed rice products.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.6
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• pp.1164-1170
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• 2001

Antimutagenic and antimicrobial effects of cucumber extracts were investigated. Antimutagenic effects of cucumber extract against aflatoxin (AFB$_1$) as indirect mutagen and N-methyl-N'-nitro-N-nitrcsoguanidine (MNNG) as direct mutagen using the Ames assay system with Salmonella typhimurium TA100 were studied. 1.25~5.0% of methanol extract exhibited 11 ~ 17% of antimutagenity against AFB$_1$ and 46~85% of antimutagenity against MNNG. Among fractions of methanol extract, hexane fraction exhibited the highest antimutagenic effect against AFB$_1$ (89%) and butanol fraction exhibited the highest antimutagenic effect against MNNG (95%). Antimicrobial effects of cucumber extract were investigated on the eleven microorganisms. Methanol extract showed anitimicrobial effect on eight microorganisms. Among these tested microorganisms, Klebsiella pnemonia KCTC 2208, pseudomonas aeruginosa KCTC 2004 were the most sensitively inhibited with 13 mm clear zone on holo test. Hexane fraction showed anitimicrobial effect only on Vibrio parahaemolyticus KCTC 2471. Chloroform and ethyl acetate fractions showed a weak effect. V. parahaemolyticus showed the lowest minium inhibitory concentration (MIC) (500 ppm) among eleven tested microorganisms by methanol extract. Sterilization effect of 1% methanol extract on P. aeruginosa incubation is 10 times stronger than 0.5% methanol extract. It estimated to need 26 min for the sterilization of 90% P. aeruginosa cell counts by 1% methanol extract but 250 min by 0.5% methanol extract.

• Toxicological Research
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• v.21 no.2
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• pp.99-105
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• 2005

Photo-mutagenic compounds have been known to alter skin cancer rates by acting as initiators or by affecting subsequent steps in carcinogenesis. The objectives of this study are to investigate the utility of photo-chromosomal aberration (photo-CA) assay for detecting photo-clastogens, and to evaluate its ability to predict rodent photocarcinogenicity. Photo-CA assay was performed with five test substances that demonstrated positive results in photo-carcinogenicity tests: 8-Methoxypsoralen (photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation), chlorpromazine (an aliphatic phenothiazine an alpha-adrenergic blocking agent), lomefloxacin (an antibiotic in a class of drugs called fluoroquinolones), anthracene (a tricyclic aromatic hydrocarbon a basic substance for production of anthraquinone, dyes, pigments, insecticides, wood preservatives and coating materials) and Retinoic acid (a retinoid compound closely related to vitamin A). For the best discrimination between the test substance-mediated genotoxicity and the undesirable genotoxicity caused by direct DNA absorption, a UV dose-response of the cells in the absence of the test substances was firstly analyzed. All 5 test substances showed a positive outcome in photo-CA assay, indicating that the photo-CA test is very sensitive to the photo-genotoxic effect of UV irradiation. With this limited data-set, an investigation into the predictive value of this photo-CA test for determining the photo-carcinogenicity showed that photo-CA assay has the high ability of a test to predict carcinogenicity. Therefore, the photo-CA test using mammalian cells seems to be a sensitive method to evaluate the photo-carcinogenic potential of new compounds.

• 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.

• Journal of Life Science
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• v.14 no.6 s.67
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• pp.925-930
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• 2004

Antioxidant activity and antimutagenic activities with and without simulated gastric digestion of hot water extracts from white and yellow onions were investigated as compared to BHT and ascorbic acid as control Contents of total phenol and flavonoid in hot water extract of yellow onion were higher than those of white one. The scavenging activity of hydrogen peroxide of both extracts were increased in direct proportion to added their concentration. Antioxidant activity and reducing power of the hot water extract were elevated through analysis of $\beta-carotene-linoleate$ system and were lower than those of BHT and ascorbic acid. Antimutagenic activity after simulated gastric digestion of hot water extract of white and yellow onions was observed against mutagen IG and MNNG on Salmonella typhimurium TA80 and TA100. Extract of yellow onion was higher in antimutagenic activity than that of white one. In conclusion, these results suggested that phenol and flavonoid in hot water extract from yellow and white onions may play an important role in the antioxidant and antimutagenic activities.

• Toxicological Research
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• v.14 no.3
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• pp.357-363
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• 1998

The teratogenic potential of the anticonvulsant drug phenytoin (PHT) has been well documented both in the human and in the experimental animals. However there are few reports on the effects of PHT on embryonic development in rats in vitro. The present study was performed to evaluate the teratogenic effects of PHT using whole-embryo culture system in rats. Sprague-Dawley rat embryos were explanted on gestational day (GD) 9.5 and cultured for 48 hrs in the immediately centrifuged and heat-inactivated rat serum containing 0,25,50, or $100{\mu}g$ PHT/mL. At the end of culture period the embryos were scored for morphological development according to the procedure of Van Maele-Fabry, and their total protein contents were determined. At 100 ${\mu}$g/mL of culture medium. PHT caused significant reduction in developmental score and protein content of embryos and a high incidence morphological abnormalities (100%). Characteristic malformations included altered yolk and embryonic circulation, craniofacial hypoplasia, neural tube schisis, branchial arch defects, abnormal ratation, and limb bud hypoplasia, among others. There were no adverse effects on embryonic growth and development at concentrations of 25 and 50 ${\mu}$g /mL of culture medium. The results indicated that the dysmorphogenic effect of PHT on cultured embryos is due to a direct interference with embryonic development.

• Toxicological Research
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• v.22 no.2
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• pp.127-133
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• 2006

Recently, we have reported that the environmental pollutant 2-bromopropane (2-BP) induces a significant embryo-fetal developmental toxicity in rats. However, the cause of developmental toxicity and the relationship between maternal and developmental toxicities could not be elucidated because the developmental toxicity of 2-BP was observed only in the presence of maternal toxicity The in vitro teratogenicity study using whole embryo culture was carried out to understand the teratogenic properties and the possible mechanism of teratogenicity induced by 2-BP in rats. Rat embryos aged 9.5 days were cultured in vitro for 48 hrs at medium concentrations of 0, 1, 3, or 10 mg/ml of 2-BP. Embryos were evaluated for growth, differentiation, and morphological alterations at the end of the culture period. At 10 mg/ml, 2-BP caused a delay in the growth and differentiation of embryos and an increase in the incidence of morphological alterations, including altered yolk sac circulation, abnormal axial rotation, craniofacial hypoplasia, open neuropore, absent optic vesicle and kinked somites. At 3 mg/ml, only a delay in the growth and differentiation of embryos was observed. There were no adverse effects on embryonic growth and development at the concentration of 1 mg/ml. The results showed that the exposure of 2-BP to rat embryos results in a developmental delay and morphological alterations at dose levels of 3 mg/ml culture media or higher and that 2-BP can induce a direct developmental toxicity in rat embryos.