Mohr Ulrich, Ernst Heinrich, Roller Markus, Pott Friedrich
Hannover Medical School, Germany.
Exp Toxicol Pathol. 2006 Aug;58(1):13-20. doi: 10.1016/j.etp.2006.06.001. Epub 2006 Jun 27.
The incidences of primary lung tumor types histologically diagnosed in 28 groups of Wistar rats of the so-called "19-dust study" are described, the total study having been already presented by Pott and Roller (Carcinogenicity study with nineteen granular dusts in rats. Eur J Oncol, 2005; 10: 249-81). Each exposed group was repeatedly instilled intratracheally with a suspension of one type and dose of 13 non-mining dusts differing in at least one of the following properties: chemical composition, density, specific surface area, and mean particle size. Eleven of the 13 dusts were classified as respirable granular bio-durable particles without known significant specific toxicity (abbreviation of the nine-word definition: GBP). In 579 (58%) lungs of 1002 rats which survived more than 26 weeks after the first instillation of GBP, at least one primary lung tumor type was observed, and in 306 (31%) at least two types. Three benign tumor types were diagnosed in the 579 tumor-bearing rats: bronchiolo-alveolar adenoma in 46%, cystic keratinizing epithelioma in 53%, and non-keratinizing epithelioma in 2.6% of the rats. Two of three malignant tumor types (bronchiolo-alveolar carcinoma and squamous cell carcinoma) occurred in 46% and 31% of the tumor-bearing rats, respectively, and adenosquamous carcinoma was diagnosed in 0.9%. Numerous lungs with a malignant tumor also showed one or more benign tumor types. In addition, single or multiple metastases from primary tumors of other sites (mainly carcinoma of the uterus) were diagnosed in 14% of the 1002 lungs. The proportionate incidences of the four predominantly diagnosed tumor types were compared with three summarized experimental groups which were exposed either to carbon black (two size classes), to titanium dioxide (two size classes), or to the total of the other nine GBP. A significant difference was not detected. The combination of dust volume with particle size correlated best with the carcinogenic effect, in contrast to dust mass and surface area.
本文描述了在所谓的“19种粉尘研究”中,对28组Wistar大鼠进行组织学诊断的原发性肺肿瘤类型的发生率,该研究的全貌已由波特和罗勒发表(大鼠对19种颗粒粉尘的致癌性研究。《欧洲肿瘤学杂志》,2005年;10:249 - 81)。每组暴露组大鼠经气管内反复滴注一种类型和剂量的13种非采矿粉尘悬浮液,这些粉尘至少在以下一种特性上有所不同:化学成分、密度、比表面积和平均粒径。13种粉尘中有11种被归类为可吸入颗粒状生物持久性颗粒,且无已知显著的特定毒性(九个词定义的缩写:GBP)。在首次滴注GBP后存活超过26周的1002只大鼠的579只(58%)肺中,观察到至少一种原发性肺肿瘤类型,306只(31%)肺中观察到至少两种类型。在579只患肿瘤大鼠中诊断出三种良性肿瘤类型:细支气管肺泡腺瘤占46%,囊性角化上皮瘤占53%,非角化上皮瘤占2.6%。三种恶性肿瘤类型中的两种(细支气管肺泡癌和鳞状细胞癌)分别出现在46%和31%的患肿瘤大鼠中,腺鳞癌的诊断率为0.9%。许多患有恶性肿瘤的肺也显示出一种或多种良性肿瘤类型。此外,在1002只大鼠的14%的肺中诊断出其他部位原发性肿瘤(主要是子宫癌)的单个或多个转移灶。将四种主要诊断出的肿瘤类型的比例发生率与三个汇总的实验组进行了比较,这三个实验组分别暴露于炭黑(两种粒径等级)、二氧化钛(两种粒径等级)或其他九种GBP的总和。未检测到显著差异。与粉尘质量和表面积相比,粉尘体积与粒径的组合与致癌作用的相关性最佳。