The Journal of toxicological sciences最新文献_第9页

Applicability of a gene expression based prediction method to SD and Wistar rats: an example of CARCINOscreen®. 基于基因表达的预测方法在SD和Wistar大鼠中的适用性:以CARCINOscreen®为例。

The Journal of toxicological sciences Pub Date : 2015-12-01 DOI: 10.2131/jts.40.805

H. Matsumoto, Fumiyo Saito, M. Takeyoshi

{"title":"Applicability of a gene expression based prediction method to SD and Wistar rats: an example of CARCINOscreen®.","authors":"H. Matsumoto, Fumiyo Saito, M. Takeyoshi","doi":"10.2131/jts.40.805","DOIUrl":"https://doi.org/10.2131/jts.40.805","url":null,"abstract":"Recently, the development of several gene expression-based prediction methods has been attempted in the fields of toxicology. CARCINOscreen® is a gene expression-based screening method to predict carcinogenicity of chemicals which target the liver with high accuracy. In this study, we investigated the applicability of the gene expression-based screening method to SD and Wistar rats by using CARCINOscreen®, originally developed with F344 rats, with two carcinogens, 2,4-diaminotoluen and thioacetamide, and two non-carcinogens, 2,6-diaminotoluen and sodium benzoate. After the 28-day repeated dose test was conducted with each chemical in SD and Wistar rats, microarray analysis was performed using total RNA extracted from each liver. Obtained gene expression data were applied to CARCINOscreen®. Predictive scores obtained by the CARCINOscreen® for known carcinogens were > 2 in all strains of rats, while non-carcinogens gave prediction scores below 0.5. These results suggested that the gene expression based screening method, CARCINOscreen®, can be applied to SD and Wistar rats, widely used strains in toxicological studies, by setting of an appropriate boundary line of prediction score to classify the chemicals into carcinogens and non-carcinogens.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"21 2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128777667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Effect of in utero exposure to endocrine disruptors on fetal steroidogenesis governed by the pituitary-gonad axis: a study in rats using different ways of administration. 子宫内暴露于内分泌干扰物对由垂体-性腺轴控制的胎儿类固醇生成的影响:一项使用不同给药方式的大鼠研究。

The Journal of toxicological sciences Pub Date : 2015-12-01 DOI: 10.2131/jts.40.909

Yudai Kariyazono, Junki Taura, Yukiko Hattori, Y. Ishii, S. Narimatsu, M. Fujimura, Tomoki Takeda, H. Yamada

{"title":"Effect of in utero exposure to endocrine disruptors on fetal steroidogenesis governed by the pituitary-gonad axis: a study in rats using different ways of administration.","authors":"Yudai Kariyazono, Junki Taura, Yukiko Hattori, Y. Ishii, S. Narimatsu, M. Fujimura, Tomoki Takeda, H. Yamada","doi":"10.2131/jts.40.909","DOIUrl":"https://doi.org/10.2131/jts.40.909","url":null,"abstract":"The effects of endocrine disruptors on testicular steroidogenesis in fetal rats were investigated in a study involving in utero exposure. In the major part of this study, pregnant rats at gestational day (GD)15 were given a single oral administration of the test substance, and then the expression of the following mRNAs in GD20 fetuses was determined: testicular steroidogenic acute-regulatory protein (StAR), a cholesterol transporter mediating the rate-limiting step of steroidogenesis, a ß-subunit of pituitary luteinizing hormone (LH), and a regulator of gonadal steroidogenesis. Among the substances tested, only di(2-ethylhexyl)phthalate (DEHP) reduced the expression of fetal testicular StAR. The others listed below exhibited little effect on fetal StAR: 2,2',4,4'-tetrabromodiphenylether, tributyltin chloride, atrazine, permethrin, cadmium chloride (Cd), lead acetate (Pb) and methylmercury (CH3HgOH). None of them, including DEHP, lacked the ability to reduce the expression of pituitary LHß mRNA. The present study also examined the potential of metals as modifiers of fetal steroidogenesis by giving them to pregnant dams in drinking water during GD1 and GD20. Under these conditions, Cd and Pb at a low concentration (0.01 ppm) significantly attenuated the fetal testicular expression of StAR mRNA without a concomitant reduction in LHß. No such effect was detected with CH3HgOH even at 1 ppm. These results suggest that: 1) DEHP, Cd and Pb attenuate the fetal production of sex steroids by directly acting on the testis, and 2) chronic treatment during the entire gestational period is more useful than a single administration for determining the hazardous effect of a suspected endocrine disruptor on fetal steroidogenesis.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125494946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

The effects of long-lasting hypoglycemia on male reproductive organs in rats. 长期低血糖对大鼠雄性生殖器官的影响。

The Journal of toxicological sciences Pub Date : 2015-12-01 DOI: 10.2131/jts.40.719

Taiki Kobayashi, Jun-ichi Namekawa, T. Shimomoto, M. Yasui, T. Iijima, Y. Itano, D. Miura, Y. Kasahara

{"title":"The effects of long-lasting hypoglycemia on male reproductive organs in rats.","authors":"Taiki Kobayashi, Jun-ichi Namekawa, T. Shimomoto, M. Yasui, T. Iijima, Y. Itano, D. Miura, Y. Kasahara","doi":"10.2131/jts.40.719","DOIUrl":"https://doi.org/10.2131/jts.40.719","url":null,"abstract":"Glucose has an important role in spermatogenesis. Nevertheless there are few reports in which the effects of long-lasting hypoglycemia on male reproductive organs have been evaluated. Therefore, insulin was administered subcutaneously at 100, 200, and 400 IU/kg to male rats twice a day for one month. This treatment regimen produced plasma glucose levels that rapidly decreased after treatment, with decreased glucose levels lasting for several hours after each administration on the first and final treatment days. During the treatment period, no abnormalities in clinical signs or body weight were observed. No statistically significant differences were noted in the weights of testes, epididymides, prostates and seminal vesicles, or pituitary glands. Histopathological examination revealed that the insulin-treated animals exhibited degeneration of seminiferous tubules in the testes and exfoliation of germ cells in the lumens of epididymides as a secondary change related to the testicular lesions. The incidences of the histopathological findings were found to be proportional to insulin dose. Sperm analysis of the group receiving the highest dosage indicated that the sperm concentration tended to decrease and the incidences of sperm malformations tended to increase. Our results suggest that long-lasting hypoglycemia affects male reproductive organs in rats.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"55 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131709472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

S-Mercuration of ubiquitin carboxyl-terminal hydrolase L1 through Cys152 by methylmercury causes inhibition of its catalytic activity and reduction of monoubiquitin levels in SH-SY5Y cells. 甲基汞通过Cys152对泛素羧基末端水解酶L1的s -汞化导致SH-SY5Y细胞中泛素羧基末端水解酶L1的催化活性抑制和单泛素水平降低。

The Journal of toxicological sciences Pub Date : 2015-12-01 DOI: 10.2131/jts.40.887

T. Toyama, Y. Abiko, Y. Katayama, T. Kaji, Y. Kumagai

{"title":"S-Mercuration of ubiquitin carboxyl-terminal hydrolase L1 through Cys152 by methylmercury causes inhibition of its catalytic activity and reduction of monoubiquitin levels in SH-SY5Y cells.","authors":"T. Toyama, Y. Abiko, Y. Katayama, T. Kaji, Y. Kumagai","doi":"10.2131/jts.40.887","DOIUrl":"https://doi.org/10.2131/jts.40.887","url":null,"abstract":"Methylmercury (MeHg) is an environmental electrophile that covalently modifies cellular proteins. In this study, we identified proteins that undergo S-mercuration by MeHg. By combining two-dimensional SDS-PAGE, atomic absorption spectrometry and ultra performance liquid chromatography mass spectrometry (UPLC/MS/MS), we revealed that ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a target for S-mercuration in human neuroblastoma SH-SY5Y cells exposed to MeHg (1 µM, 9 hr). The modification site of UCH-L1 by MeHg was Cys152, as determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. MeHg was shown to inhibit the catalytic activity of recombinant human UCH-L1 in a concentration-dependent manner. Knockdown of UCH-L1 indicated that this enzyme plays a critical role in regulating mono-ubiquitin (monoUb) levels in SH-SY5Y cells and exposure of SH-SY5Y cells to MeHg caused a reduction in the level of monoUb in these cells. These observations suggest that UCH-L1 readily undergoes S-mercuration by MeHg through Cys152 and this covalent modification inhibits UCH-L1, leading to the potential disruption of the maintenance of cellular monoUb levels.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"172 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124200734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Disruption of spindle checkpoint function ahead of facilitation of cell proliferation by repeated administration of hepatocarcinogens in rats. 反复给药肝致癌物在促进大鼠细胞增殖之前破坏梭形检查点功能。

The Journal of toxicological sciences Pub Date : 2015-12-01 DOI: 10.2131/jts.40.855

M. Kimura, S. Mizukami, Yousuke Watanabe, Yasuko Hasegawa-Baba, N. Onda, Toshinori Yoshida, M. Shibutani

{"title":"Disruption of spindle checkpoint function ahead of facilitation of cell proliferation by repeated administration of hepatocarcinogens in rats.","authors":"M. Kimura, S. Mizukami, Yousuke Watanabe, Yasuko Hasegawa-Baba, N. Onda, Toshinori Yoshida, M. Shibutani","doi":"10.2131/jts.40.855","DOIUrl":"https://doi.org/10.2131/jts.40.855","url":null,"abstract":"We aimed to clarify the hepatocarcinogen-specific disruption of cell cycle checkpoint functions and its time course after repeated administration of hepatocarcinogens. Thus, rats were repeatedly administered with hepatocarcinogens (methapyrilene, carbadox and thioacetamide), a marginal hepatocarcinogen (leucomalachite green), hepatocarcinogenic promoters (oxfendazole and β-naphthoflavone) or non-carcinogenic hepatotoxicants (promethazine and acetaminophen) for 7, 28 or 90 days, and the temporal changes in cell proliferation, expression of G1/S and spindle checkpoint-related molecules, and apoptosis were examined using immunohistochemistry and/or real-time RT-PCR analysis. Hepatocarcinogens facilitating cell proliferation at day 28 of administration also facilitated cell proliferation and apoptosis at day 90. Hepatocarcinogen- or hepatocarcinogenic promoter-specific cellular responses were not detected by immunohistochemical single molecule analysis even after 90 days. Expression of Cdkn1a, Mad2l1, Chek1 and Rbl2 mRNA also lacked specificity to hepatocarcinogens or hepatocarcinogenic promoters. In contrast, all hepatocarcinogens and the marginally hepatocarcinogenic leucomalachite green induced Mdm2 upregulation or increase in the number of phosphorylated MDM2(+) cells from day 28, irrespective of the lack of cell proliferation facilitation by some compounds. However, different Tp53 expression levels suggest different mechanisms of induction or activation of MDM2 among hepatocarcinogens. On the other hand, hepatocarcinogenic methapyrilene and carbadox downregulated the number of both ubiquitin D(+) cells and proliferating cells remaining in M phase at day 28 and/or day 90, irrespective of the lack of cell proliferation facilitation in the latter. These results suggest that hepatocarcinogens disrupt spindle checkpoint function after 28 or 90 days of administration, which may be induced ahead of cell proliferation facilitation.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116880638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Androgen receptor functions as a negative transcriptional regulator of DEPTOR, mTOR inhibitor. 雄激素受体是detor、mTOR抑制剂的负转录调控因子。

The Journal of toxicological sciences Pub Date : 2015-12-01 DOI: 10.2131/jts.40.753

Yuichiro Kanno, Shuai Zhao, Naoya Yamashita, K. Yanai, K. Nemoto, Y. Inouye

{"title":"Androgen receptor functions as a negative transcriptional regulator of DEPTOR, mTOR inhibitor.","authors":"Yuichiro Kanno, Shuai Zhao, Naoya Yamashita, K. Yanai, K. Nemoto, Y. Inouye","doi":"10.2131/jts.40.753","DOIUrl":"https://doi.org/10.2131/jts.40.753","url":null,"abstract":"It has been noticed that crosstalk between androgen receptor (AR) and mammalian target of rapamycin (mTOR) signaling pathways plays a crucial role in the proliferation of prostate cancer cells. To clarify this mechanism, we focused on DEPTOR, a naturally occurring inhibitor of mTOR. The treatment of a human AR-positive prostate cancer cell line, LNCaP, with the AR-agonist dihydrotestosterone (DHT) repressed DEPTOR mRNA expression in a time-dependent manner. This repression was abrogated by treatment with the AR-antagonist bicalutamide. Knockdown of DEPTOR mRNA by siRNA resulted in the increased phosphorylation of 70 kDa ribosomal protein S6 kinase 1 (S6K), a substrate of mTORC1, accompanied by the elevated expression of cyclin D1, a positive regulator of cell proliferation. Furthermore, the ChIP assay demonstrated that AR could bind to AR-responsible element-like region within the 4th intron of the DEPTOR gene. The amount of acetylated histone H3 (Lys9, Lys14) was reduced by the DHT treatment in this region. Taken together, these results propose that AR-dependent prostate cancer cell proliferation requires decreased DEPTOR transcription directly controlled by AR.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"67 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125892299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Understanding dabs: contamination concerns of cannabis concentrates and cannabinoid transfer during the act of dabbing. 了解轻拍:在轻拍过程中大麻浓缩物和大麻素转移的污染问题。

The Journal of toxicological sciences Pub Date : 2015-12-01 DOI: 10.2131/jts.40.797

J. Raber, Sytze Elzinga, C. Kaplan

{"title":"Understanding dabs: contamination concerns of cannabis concentrates and cannabinoid transfer during the act of dabbing.","authors":"J. Raber, Sytze Elzinga, C. Kaplan","doi":"10.2131/jts.40.797","DOIUrl":"https://doi.org/10.2131/jts.40.797","url":null,"abstract":"Cannabis concentrates are gaining rapid popularity in the California medical cannabis market. These extracts are increasingly being consumed via a new inhalation method called 'dabbing'. The act of consuming one dose is colloquially referred to as \"doing a dab\". This paper investigates cannabinoid transfer efficiency, chemical composition and contamination of concentrated cannabis extracts used for dabbing. The studied concentrates represent material available in the California medical cannabis market. Fifty seven (57) concentrate samples were screened for cannabinoid content and the presence of residual solvents or pesticides. Considerable residual solvent and pesticide contamination were found in these concentrates. Over 80% of the concentrate samples were contaminated in some form. THC max concentrations ranged from 23.7% to 75.9% with the exception of one outlier containing 2.7% THC and 47.7% CBD. Up to 40% of the theoretically available THC could be captured in the vapor stream of a dab during inhalation experiments. Dabbing offers immediate physiological relief to patients in need but may also be more prone to abuse by recreational users seeking a more rapid and intense physiological effect.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133780558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 170

Methylmercury can induce Parkinson's-like neurotoxicity similar to 1-methyl-4- phenylpyridinium: a genomic and proteomic analysis on MN9D dopaminergic neuron cells. 甲基汞可以诱导类似于1-甲基-4-苯基吡啶的帕金森样神经毒性:MN9D多巴胺能神经元细胞的基因组和蛋白质组学分析。

The Journal of toxicological sciences Pub Date : 2015-12-01 DOI: 10.2131/jts.40.817

Yueting Shao, D. Figeys, Zhibin Ning, R. Mailloux, H. Chan

{"title":"Methylmercury can induce Parkinson's-like neurotoxicity similar to 1-methyl-4- phenylpyridinium: a genomic and proteomic analysis on MN9D dopaminergic neuron cells.","authors":"Yueting Shao, D. Figeys, Zhibin Ning, R. Mailloux, H. Chan","doi":"10.2131/jts.40.817","DOIUrl":"https://doi.org/10.2131/jts.40.817","url":null,"abstract":"Exposure to environmental chemicals has been implicated as a possible risk factor for the development of neurodegenerative diseases. Our previous study showed that methylmercury (MeHg) exposure can disrupt synthesis, uptake and metabolism of dopamine similar to 1-methyl-4-phenylpyridinium (MPP(+)). The objective of this study was to investigate the effects of MeHg exposure on gene and protein profiles in a dopaminergic MN9D cell line. MN9D cells were treated with MeHg (1-5 μM) and MPP(+) (10-40 μM) for 48 hr. Real-time PCR Parkinson's disease (PD) arrays and high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) were performed for the analysis. PD PCR array results showed that 19% genes were significantly changed in the 2.5 μM MeHg treated cells, and 39% genes were changed in the 5 μM MeHg treated cells. In comparison, MPP(+) treatment (40 µM) resulted in significant changes in 25% genes. A total of 15 common genes were altered by both MeHg and MPP(+), and dopaminergic signaling transduction was the most affected pathway. Proteomic analysis identified a total of 2496 proteins, of which 188, 233 and 395 proteins were differentially changed by 1 μM and 2.5 μM MeHg, and MPP(+) respectively. A total of 61 common proteins were changed by both MeHg and MPP(+) treatment. The changed proteins were mainly involved in energetic generation-related metabolism pathway (propanoate metabolism, pyruvate metabolism and fatty acid metabolism), oxidative phosphorylation, proteasome, PD and other neurodegenerative disorders. A total of 7 genes/proteins including Ube2l3 (Ubiquitin-conjugating enzyme E2 L3) and Th (Tyrosine 3-monooxygenase) were changed in both genomic and proteomic analysis. These results suggest that MeHg and MPP(+) share many similar signaling pathways leading to the pathogenesis of PD and other neurodegenerative diseases.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133546951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 27

Association of A118G polymorphism in the μ-opioid receptor gene with smoking behaviors: a meta-analysis. μ-阿片受体基因A118G多态性与吸烟行为的关联:一项meta分析

The Journal of toxicological sciences Pub Date : 2015-12-01 DOI: 10.2131/jts.40.711

Juan Wang, P. Jin, Wenhui Wang, Mei He, Zixue Zhang, Y. Liu

{"title":"Association of A118G polymorphism in the μ-opioid receptor gene with smoking behaviors: a meta-analysis.","authors":"Juan Wang, P. Jin, Wenhui Wang, Mei He, Zixue Zhang, Y. Liu","doi":"10.2131/jts.40.711","DOIUrl":"https://doi.org/10.2131/jts.40.711","url":null,"abstract":"Many studies have investigated the association between the A118G polymorphism in the μ-opioid receptor gene and smoking behaviors, but the results remain controversial. This meta-analysis aimed to derive a more reliable estimate of the effect of the A118G polymorphism on smoking behaviors. We systematically searched the PubMed/Medline, Embase and Web of Science databases for eligible articles published up to October 23, 2014. A total of six studies were selected. Odds ratios (ORs) as well as their corresponding 95% confidence intervals (CIs) were used to estimate the association between A118G polymorphism and smoking behaviors in four genetic models. Heterogeneity analysis and publication bias were also performed. Subgroup analysis was conducted according to different ethnicities. The meta-analysis was performed using either a fixed- or random-effects model as deemed appropriate. In the result of the meta-analysis, a significant association was detected in the dominant model in the Caucasian subgroup (OR = 3.26, 95% CI = 2.65-4.05). This result indicated that Caucasians carrying the G allele (AG + GG) of the A118G polymorphism in the μ-opioid receptor gene were more likely to be addicted to smoking compared with those with the AA homozygote. However, no significant association was found in other genetic models.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131264681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Evaluation of skin phototoxicity study using SD rats by transdermal and oral administration. 经皮和口服给药对SD大鼠皮肤光毒性研究的评价。

The Journal of toxicological sciences Pub Date : 2015-12-01 DOI: 10.2131/jts.40.667

Y. Yonezawa, Tomoka Ohsumi, Taishi Miyashita, Akira Kataoka, Kazuto Hashimoto, H. Nejishima, H. Ogawa

{"title":"Evaluation of skin phototoxicity study using SD rats by transdermal and oral administration.","authors":"Y. Yonezawa, Tomoka Ohsumi, Taishi Miyashita, Akira Kataoka, Kazuto Hashimoto, H. Nejishima, H. Ogawa","doi":"10.2131/jts.40.667","DOIUrl":"https://doi.org/10.2131/jts.40.667","url":null,"abstract":"Guinea pigs are the most frequently used animals in phototoxicity studies. However, general toxicity studies most often use Sprague-Dawley (SD) rats. To reduce the number of animals needed for drug development, we examined whether skin phototoxicity studies could be performed using SD rats. A total of 19 drugs that had previously been shown to have phototoxic potential and 3 known phototoxic compounds were administered transdermally to guinea pigs and SD rats. Eleven of the potentially phototoxic drugs and 2 of the known phototoxic compounds were also administered orally to guinea pigs and SD rats. After administration, the animals were irradiated with UV-A (10 J/cm(2)) and UV-B (0.25 J/cm(2) in guinea pigs and 0.031 J/cm(2) in SD rats) with doses based on standard phototoxicity study guidelines and the results of a minimum erythema dose test, respectively. In the transdermal administration study, all of the known phototoxic compounds and 7 of the drugs induced phototoxic reactions. In the oral administration study, both known phototoxic compounds and 5 drugs induced phototoxic reactions in both species; one compound each was found to be toxic only in SD rats or guinea pigs. The concordance rate of guinea pigs and SD rats was 100% in the transdermal administration study and 85% in the oral administration study. This study demonstrated that phototoxicity studies using SD rats have the same potential to detect phototoxic compounds as studies using guinea pigs.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"62 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125382508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15