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十二烷基苯经皮肤涂抹对无毛小鼠致癌作用和致瘤作用的研究。

Studies of the carcinogenesis and tumorigenesis of skin applications of dodecylbenzene on hairless mice.

作者信息

Iversen O H

机构信息

Institute of Pathology, University of Oslo, Norway.

出版信息

Br J Ind Med. 1989 Sep;46(9):608-16. doi: 10.1136/oem.46.9.608.

Abstract

Dodecylbenzene in various concentrations, dissolved in acetone to a final volume of 50 microliters, was applied twice a week for 78 weeks to the back skin of hairless mice, with or without pretreatment with 51.2 micrograms 9,10-dimethyl-1,2-benzanthracene (DMBA). A negative control group was painted with acetone only and a positive control group was given a single application of 51.2 micrograms DMBA. A few tumours developed but there was no significant skin tumorigenicity--that is, occurrence of benign or malignant tumours--by acetone alone, or by 16% dodecylbenzene. More tumours developed in the group treated with 80% dodecylbenzene than in the group treated with acetone alone or with 16% dodecylbenzene, but there was no significant difference between treatments with 16% and 80% dodecylbenzene. There was only a suggestive increase in tumorigenesis in the group given 51.2 micrograms DMBA and thereafter painted with 40% dodecylbenzene twice a week compared with the group given 51.2 micrograms DMBA once. As regards histologically malignant tumours--that is, carcinogenicity--the group treated twice a week with 16% dodecylbenzene alone developed two skin malignancies, whereas only one carcinoma was observed in the group treated with 80% dodecylbenzene; both results are non-significant. There was only a suggestive increase in the occurrence of skin malignancies in the group treated with DMBA followed by 40% dodecylbenzene compared with that treated with DMBA alone. As regards other tumours, treatment with 80% dodecylbenzene led to six lymphomas in 56 animals, whereas the acetone control group had two lymphomas in 56 animals, a difference which is only suggestive. DMBA alone and DMBA followed by dodecylbenzene gave five and four lymphomas, respectively. There was no significant difference between controls and dodecylbenzene painted animals for lung adenomas or other tumours. A pronounced epidermal hyperplasia, an increase in melanin pigment ("blue spots"), pigment leakage, and skin ulcerations were seen, mainly after 80% dodecylbenzene and after DMBA followed by 40% dodecylbenzene. There was no obvious increase in amyloidosis after continual treatment with 80% dodecylbenzen. The results indicate that 80% dodecylbenzene alone is weakly tumorigenic but not carcinogenic in the skin of hairless mice, and it tends slightly to enhance DMBA initiated tumorigenesis and carcinogenesis. Dodecylbenzene may be a weak inducer of malignant lymphomas. It is a fairly strong skin irritant and may increase amyloidosis.

摘要

将不同浓度的十二烷基苯溶解于丙酮中,使其最终体积达到50微升,每周两次涂抹于无毛小鼠的背部皮肤,持续78周,涂抹时小鼠或预先用51.2微克的9,10 - 二甲基 - 1,2 - 苯并蒽(DMBA)处理,或未作预处理。阴性对照组仅涂抹丙酮,阳性对照组单次涂抹51.2微克DMBA。单独使用丙酮或16%的十二烷基苯时,虽有少数肿瘤发生,但无明显的皮肤致瘤性,即未出现良性或恶性肿瘤。与单独使用丙酮或16%十二烷基苯处理的组相比,80%十二烷基苯处理的组出现了更多肿瘤,但16%和80%十二烷基苯处理组之间无显著差异。与仅单次给予51.2微克DMBA的组相比,给予51.2微克DMBA后每周两次涂抹40%十二烷基苯的组,肿瘤发生仅略有增加。就组织学上的恶性肿瘤而言,即致癌性,单独每周两次用16%十二烷基苯处理的组出现了两例皮肤恶性肿瘤,而80%十二烷基苯处理的组仅观察到一例癌;两者结果均无统计学意义。与仅用DMBA处理的组相比,用DMBA后再用40%十二烷基苯处理的组,皮肤恶性肿瘤的发生仅略有增加。就其他肿瘤而言,80%十二烷基苯处理使56只动物中有6只发生淋巴瘤,而丙酮对照组的56只动物中有2只发生淋巴瘤,这种差异仅具有提示性。单独使用DMBA以及先用DMBA后用十二烷基苯处理的组分别有5例和4例淋巴瘤。对于肺腺瘤或其他肿瘤,对照组与涂抹十二烷基苯的动物组之间无显著差异。主要在使用80%十二烷基苯后以及先用DMBA后再用40%十二烷基苯处理后,可见明显的表皮增生、黑色素沉着增加(“蓝斑”)、色素渗漏和皮肤溃疡。连续用80%十二烷基苯处理后,淀粉样变无明显增加。结果表明,单独使用80%十二烷基苯在无毛小鼠皮肤中具有弱致瘤性但无致癌性,且它略微倾向于增强由DMBA引发的肿瘤发生和致癌作用。十二烷基苯可能是恶性淋巴瘤的弱诱导剂。它是一种较强的皮肤刺激物,可能会增加淀粉样变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7a4/1009835/ee25a439c42a/brjindmed00137-0022-a.jpg

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