• Title/Summary/Keyword: indirect mutagen

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Phototoxicity: Its Mechanism and Animal Alternative Test Methods

  • Kim, Kyuri;Park, Hyeonji;Lim, Kyung-Min
    • Toxicological Research
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    • v.31 no.2
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    • pp.97-104
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    • 2015
  • The skin exposure to solar irradiation and photoreactive xenobiotics may produce abnormal skin reaction, phototoxicity. Phototoxicity is an acute light-induced response, which occurs when photoreacive chemicals are activated by solar lights and transformed into products cytotoxic against the skin cells. Multifarious symptoms of phototoxicity are identified, skin irritation, erythema, pruritis, and edema that are similar to those of the exaggerated sunburn. Diverse organic chemicals, especially drugs, are known to induce phototoxicity, which is probably from the common possession of UV-absorbing benzene or heterocyclic rings in their molecular structures. Both UVB (290~320 nm) and UVA (320~400 nm) are responsible for the manifestation of phototoxicity. Absorption of photons and absorbed energy (hv) by photoactive chemicals results in molecular changes or generates reactive oxygen species and depending on the way how endogenous molecules are affected by phototoxicants, mechanisms of phototoxcity is categorized into two modes of action: Direct when unstable species from excited state directly react with the endogenous molecules, and indirect when endogeneous molecules react with secondary photoproducts. In order to identify phototoxic potential of a chemical, various test methods have been introduced. Focus is given to animal alternative test methods, i.e., in vitro, and in chemico assays as well as in vivo. 3T3 neutral red uptake assay, erythrocyte photohemolysis test, and phototoxicity test using human 3-dimensional (3D) epidermis model are examples of in vitro assays. In chemico methods evaluate the generation of reactive oxygen species or DNA strand break activity employing plasmid for chemicals, or drugs with phototoxic potential.

Antimutagenic Effect of Extract of Platycodon grandiflorum (장생 도라지(Platycodon grandiflorum) )추출물의 돌연변이 억제효과)

  • Shon, Mi-Yae;Seo, Jong-Kwon;Kim, Haeng-Ja;Sung, Nak-Ju
    • Korean Journal of Food Science and Technology
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    • v.33 no.6
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    • pp.651-655
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    • 2001
  • To investigate the antimutagenic effect of Platycodon grandiflorum DC, methanol extract of Platycodon grandiflorum DC was investigated. In Ames test, the methanol extract showed inhibitory effects of 80-90% on the mutagenicity induced by indirect mutagen of IQ(2-amino-3-methylimidazo[4,5-f]quinoline) and direct mutatgen of MNNG(N-methyl-N'-nitro-N-nitrosoguanidine) in Salmonella typhimurium TA 98 and TA 100. And then the methanol extract was further fractionated. Among the solvent extracted fractions from the methanol extract, the ethyl acetate fraction and butanol fraction exhibited the greatest antimutagenic effect suppressing the mutagenicity IQ and MNNG with inhibition rate of 99% and 98%.

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Antimutagenic Effect and Cytotoxicity to Human Cancer Cell Lines of Colored Potato Extracts (유색감자 추출물의 항돌연변이 및 항암 활성)

  • Park, Young-Eun;Jeong, Jin-Cheol;Cho, Huyn-Mook;Hwang, Young-Sun;Lee, Hyeon-Jin;Choi, Su-San-Na;Lee, Su-Jin;Park, Eun-Sun;Ko, Eun-A;Kim, Nan-Sol;Lim, Jung-Dae;Choung, Myoung-Gun
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.53 no.1
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    • pp.75-84
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    • 2008
  • Colored potatoes are an excellent source of dietary polyphenols including anthocyanins. Generally, anthocyanins from fruits and vegetables exhibit anti-carcinogenesis and anti-cancer properties in vitro test. This experiment was conducted to know the effects of colored potato extracts contained anthocyanins on antimutagenic activity and anticancer activity to six human cancer cell lines containing LNCaP (androgen-dependent) prostate cancer cells. Extracts of three colored potatoes ('Hongyoung', 'Jayoung' and 'Jasim') and the white potato ('Superior') cultivars were used in this study. The extracts of three colored potatoes inhibited the mutagenicities induced by direct mutagen such as 4-nitro-quinoline-1-oxide (4-NQO) and another indirect mutagens of bezo(a)pyrene (BaP). Also, the extracts of 'Hoyoung' and 'Jayoung' showed higher antimutagenic activity than 'Jasim' and 'Superior' against to direct or indirect mutagen on both strains of TA98 and TA100. The activity of growth-inhibitory of extract of four potato cultivars were screened by SRB (sulphorhodamine B) method on diverse human cancer cells representing different types of cancers. Among the extract of four potato cultivars, the extract of 'Jasim' showed moderate inhibition on proliferation of LNCaP, ACHN and MOLT-4F cells and did not inhibit the proliferation of other cancer cells. On the other hand, extract of 'Superior' did not inhibit the proliferation of any tested cancer cell lines. However, the extracts of 'Hongyoung and Jayoung' inhibited the proliferation of cancer cells with $GI_{50}$ values ranging from 2.5 to $30\;{\mu}g/mL$. On the basis of the $GI_{50}$ values, it is clear that LNCaP cells were more sensitive to extracts of colored potato cultivars than other cancer cells. The extract of 'Jayoung' at $30\;{\mu}g/mL$ were more active and inhibited cell proliferation, and induced apoptosis in LNCaP cells. This result revealed that the extracts of colored potatoes are expected to be good candidate for development into source of antimutagenic and anticancer agent.

Molecular Basis of Organospecific Carcinogensis by Chemical Carcinogens-Study with Breast Cancer Specific Carcinogens: DMBA as an Indirect-Acting carcinogen and NMU as a Direct-Acting cancinogen. (화학적 발암원의 조직 특이성 암유발기전 - DMBA와 NMU의 선택적 유암 발생기전을 중심으로 )

  • 박종영;김승원;박상철
    • Environmental Mutagens and Carcinogens
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    • v.9 no.1
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    • pp.1-12
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    • 1989
  • To study the selective organospecific carcinogenesis by the specific chemical carcinogens, the breast cancer induction model by oral administration of 7, 12-dimethylbenzanthracene (DMBA) or by intravenous injection of N-methylni-trosourea (NMU) on female rats was analyzed. In the present experiment, we compared the effexts of ages on the chemical mammary carcinogenesis by studying the metabolic system of the carcinogenic activation, detoxification or DNA damage and repair. The breast tumor incidence was significantly higher in the young rats of 50 days old than in those of one year old rats. As an index of organospecific DNA damage or repair, the in vivo covalent binding index(CBI) of the specific organs by the specific chemical carcinogens was monitored. And for the analysis of carcinogenic activation, the quantity of cytochrome P450`s was determined with the respective type-specific monoclonal antibody, while the detoxication capacity was deduced by the activity monitoring of glutathione S-transferase (GST) and peroxidase. The skin tissues of the mammary region had the highest CBI with both of DMBA and NMU at 50 days of age. And there were contrasting differences in the contents of carcinogenic activation and detoxication system: that is, the content of T.C.D.D.-inducible cytochrome P450 was high, while the activities of GST and peroxidase was low in the mammary skin tissues at tumor prevalent age. These results led us to conclude that the molecular organospecific carcinogenesis, as illustrated with mammary carcinoge-nesis by DMBA and NMU, is operated probably through the differential capacity of the target tissues in the high carcinogenic activation, low detoxication and the low DNA repair function.

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Antimutagenic Effects of Extracts of Curry Powder and Its Individual Spice (카레분 및 향신료 추출물의 항 돌연변이 효과)

  • 정승현;정명수;이진선;박기문
    • Food Science of Animal Resources
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    • v.22 no.4
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    • pp.352-357
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    • 2002
  • Antimutagenic effects of extracts from curry powder and its individual fourteen kinds of spices, were investigated by Ames test. The antimutagenic effects against a direct mutagen, 2-nitrofluorene(2 -NF) and two indirect mutagens, 2-anthramine(2-AT) and 2-acetamidofluorene (2-AE) in the S. typhimurium TA98 were tested. For the 2-NF, the antimutagenicity of cinnamon, fenugreek, fennel, ginger, clove, turmeric and celery seed were determined as 42, 38, 32, 28, 24, 23 and 20%, respectively. The antimutagenicity of clove against the 2-AT was the highest (116%), and followed by the order of celery seed(103%), cardamon(100%), red pepper(99%), cinnamon(92%), cumin(83%), ginger(82%), fennel(82%), coriander (71%), nutmeg(68%) and turmeric (55%). The results also showed that the antimutagenic effect of clove against the 2-AF was superior to other spices. In case of curry powder among more than 10 kinds of spices, the antimutagenenicity against the 2-AT and 2-AF showed 23% and 6%, respectively, but no effect was observed against the 2-NF.

In vitro Antimutagenic Activity of Chitosan and Its Bio-antimutagenic Characteristics (Chitosan의 in vitro 돌연변이 억제효과 및 세포내 작용 특성)

  • Chun, Hyang-Sook;Chang, Hyun-Joo;Lee, Jong-Mi
    • Korean Journal of Food Science and Technology
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    • v.28 no.6
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    • pp.1059-1064
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    • 1996
  • The inhibitory effects of chitosan on mutagenicity induced by 3-amino-1-methyl-5H-pyrido [4,3-b] indole (Trp-P-2), sodium azide (SA), 2-nitrofluorene (2-NF), and 4-nitroquinoline oxide (4-NQO) were investigated using Salmonella typhimurium reversion assay and SOS Chromotest. In Salmonella typhimurium reversion assay. Chitosan showed 24-65% of inhibitory effect against the mutagenicity of an indirect-acting mutagen, Trp-P-2. On the other hand, no inhibitory effect was observed against the mutagenicity of direct-acting mutagens (2-NF, SA). In SOS chromotest. chitosan showed 46-49% effects on SOS function induced by 4-NQO. Chitosan inhibited the mutagenicity induced by Trp-P-2 with 9-39% of inhibition rate. It was also evaluated whether inhibitory effect of chitosan is due to its bio-antimutagenic or desmutagenic action. Chitosan at high concentrations showed a bio-antimutagenicity with dose-dependent manner, but it showed a desmutagenicity at low concentrations against the mutation induced by Trp-P-2.

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Antimutagenic Effect of Extract of Eleutherococcus senticosus Maxim (가시오갈피 추출물의 항돌연변이 효과)

  • Park, Jeong-Seob;Oh, Chan-Ho;Koh, Ha-Young;Choi, Dong-Seong
    • Korean Journal of Food Science and Technology
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    • v.34 no.6
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    • pp.1110-1114
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    • 2002
  • Antimutagenic effect of Eleutherococcus senticosus Maxim. on the mutagenicity induced by 2-AF and Trp-P-1 was studied using the Ames test with Salmonella typhimurium TA98 and TA100. In S. typhimurium TA98, the methanol extract $(500\;{\mu}g/plate)$ of root, stem, and leaf of E. senticosus showed inhibitory effects of 72.8, 70.0, and 78.7% on the mutagenicity induced by 2-AF, and 69.2, 64.9, and 59.4% by Trp-P-1, respectively, whereas none was observed in S. typhimurium TA100. These results suggest that the methanol extract of E. senticosus inhibits a frame shift mutation. And then the methanol extract further fractionated by chloroform, butanol, and water. The chloroform fractions of root, stem, and leaf showed strong antimutagenic effects induced by 2-AF and Trp-P-1 in S. typhimurium TA98, whereas none was observed in the butanol and aqueous fractions. The chloroform fractions of root, stem, and leaf showed antimutagenic effects of $13{\sim]92%$ in a dose-dependent manner.