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Establishment and Validation of an Ultra-Short-Term Skin Carcinogenicity Bioassay Using Tg-rasH2 Mice.
Veterinary Pathology ( IF 2.4 ) Pub Date : 2019-06-20 , DOI: 10.1177/0300985819854440
Mayumi Kawabe 1 , Koji Urano 2 , Mayuko Suguro 1 , Tomomi Hara 1 , Yasushi Kageyama 3 , Yukinori Mera 1 , Hideki Tsutsumi 2
Affiliation  

After initiation with 7,12-dimethylbenz[a]anthracene (DMBA), the promoting potential of 12-O-tetradecanoylphorbol-13-acetate (TPA) on skin tumor development can be detected by an ultra-short-term skin carcinogenicity bioassay using Tg-rasH2 mice. In the present study, 10 chemicals were assessed using this ultra-short-term bioassay as a first step to validate this practical and easy-to-use skin carcinogenicity bioassay. These chemicals belonged to 4 categories: dermal vehicles (acetone, 99.5% ethanol, anhydrous ethanol, and Vaseline), skin noncarcinogens (oleic acid diethanolamine condensate, benzethonium chloride, and diisopropylcarbodiimide), skin tumor promoters (TPA and benzoyl peroxide), and a skin carcinogen (4-vinyl-1-cyclohexene diepoxide). In a first study, DMBA was used as the initiator at a dose of 50 μg according to previous data, but skin tumors were observed in the no-treatment and vehicle groups. Therefore, the dose of DMBA for skin tumor initiation was reevaluated using 12.5 or 25 μg, with 12.5 μg found to be sufficient for initiation activity. In the ultra-short-term assay, the vehicles and skin noncarcinogens were negative while the skin tumor promoters and the skin carcinogen were positive. The detection of skin tumor promotion and carcinogenicity was feasible in only 8 weeks. In conclusion, this carcinogenicity bioassay may represent a useful tool for the assessment of the carcinogenicity potential of topically applied chemicals.

中文翻译:

Tg-rasH2小鼠超短期皮肤致癌性生物测定的建立和验证。

用7,12-二甲基苯并[a]蒽(DMBA)引发后,可通过超短期皮肤致癌性生物测定法检测12-O-十四烷酰phorbol-13-乙酸盐(TPA)对皮肤肿瘤发展的促进潜力。 Tg-rasH2小鼠。在本研究中,使用该超短期生物测定法评估了10种化学物质,作为验证该实用且易于使用的皮肤致癌性生物测定法的第一步。这些化学物质分为4类:皮肤媒介物(丙酮,99.5%乙醇,无水乙醇和凡士林),皮肤非致癌物(油酸二乙醇胺缩合物,苄索氯铵和二异丙基碳二亚胺),皮肤肿瘤促进剂(TPA和过氧化苯甲酰)和皮肤致癌物(4-乙烯基-1-环己烯二环氧)。在先前的研究中,根据先前的数据,DMBA以50μg的剂量用作引发剂,但未治疗组和媒介组均观察到皮肤肿瘤。因此,使用12.5或25μg重新评估DMBA用于皮肤肿瘤起始的剂量,发现12.5μg对于起始活性是足够的。在超短期分析中,媒介物和皮肤非致癌物为阴性,而皮肤肿瘤促进剂和皮肤致癌物为阳性。仅在8周内就可以检测到皮肤肿瘤的促进作用和致癌性。总之,这种致癌性生物测定法可能是评估局部使用化学品致癌性潜力的有用工具。在超短期分析中,媒介物和皮肤非致癌物为阴性,而皮肤肿瘤促进剂和皮肤致癌物为阳性。仅在8周内就可以检测到皮肤肿瘤的促进作用和致癌性。总之,这种致癌性生物测定法可能是评估局部使用化学品致癌性潜力的有用工具。在超短期分析中,媒介物和皮肤非致癌物为阴性,而皮肤肿瘤促进剂和皮肤致癌物为阳性。仅在8周内就可以检测到皮肤肿瘤的促进作用和致癌性。总之,这种致癌性生物测定法可能是评估局部使用化学品致癌性的有用工具。
更新日期:2019-11-01
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