Cytopathological characteristics for provoked lesions of squamous epithelia of digestive system in animal models

V. Shestakova, L. Nigmatullina, I. Atadzhanov, S. Donskov, Yu. Kozlovskaya, I. Dolgopolov, M. Rykov
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Abstract

Purpose of the study. Investigation of morphological characteristics of changes in the epithelium of foregut in experimental animals put under conditions of provoked carcinogenesis.Materials and methods. The method of chronic experiment on animals is applied: 40 female non-linear white rats, which are divided into 4 equal groups (n = 10). The first (I) and second (II) control groups of animals were exposed to mechanical trauma of the oral mucosa with additional application of 0.9 % NaCl solution and 1 % aqueous dimethyl sulfoxide (DMSO) solution with a frequency of 2 times a week. The third group of animals, i.e. the main group (4-NQO), was subjected to mechanical traumatization of the oral mucosa with additional application of 1 % DMSO aqueous solution containing 0.1 mg/ml of 4 nitroquinoline-N-oxide, with a frequency of 2 times a week. The fourth group of animals was intact. On the 1st, 7th, 10th, 14th day from the beginning of the experiment, and then every 14 days, cytological material was taken from the oral mucosa and stained with Papanicolaou stain. To compare the emerging changes, the histological picture of the organs of the foregut was studied.Results. Animals from the main group (4-NQO) showed a lag in body weight gain over the standard variance in the control (I and II) and intact groups. Atypical cells of indeterminate significance appeared in smears starting from 42 days of the experiment. Starting from the 56th day of the experiment, atypical cells (1–2 in the field of view), described in Bethesda terms as low-grade intraepithelial lesions, were detected in smears obtained from the main group of animals (4-NQO). Parabasal cells of the squamous epithelium with atypical large (more than 3 times compared to the reference) nuclei, anisonucleosis, with variable contours of the nuclear membrane within one cell, coarse chromatin were recognized as diagnostically significant.Conclusion. The severity of morphological changes in foregut epithelium in the direction of the precancerous state is significantly higher in the main group with prolonged exposure to carcinogenic factor, compared with the control and intact groups (р < 0.05). Thus, the effectiveness of modeling the conditions of provocation of carcinogenesis of the epithelium of the upper digestive tube in experimental animals was studied and proved by mechanical traumatization of the oral mucosa with additional application of carcinogen (4-NQO). This model of provocation of carcinogenesis will be used in the next study of neoplastic processes of the female reproductive system.
动物模型消化系统鳞状上皮诱发性病变的细胞病理学特征
研究目的:诱发性癌变条件下实验动物前肠上皮形态变化的研究。材料和方法。采用动物慢性实验方法:雌性非线性大鼠40只,随机分为4组(n = 10)。第一(I)组和第二(II)组动物在机械损伤口腔黏膜的基础上,添加0.9% NaCl溶液和1%二甲基亚砜(DMSO)水溶液,频率为每周2次。第三组,即主组(4- nqo),对口腔黏膜进行机械损伤,外加1% DMSO水溶液(含0.1 mg/ml 4硝基喹啉- n -氧化物),频率为每周2次。第四组动物完好无损。实验开始后第1、7、10、14天,每隔14天取口腔黏膜细胞学材料,进行帕氏染色。为了比较新出现的变化,我们研究了前肠器官的组织学图像。主组(4-NQO)的动物在体重增加方面比对照组(I和II)和完整组的标准方差滞后。从实验第42天开始,在涂片中出现意义不确定的非典型细胞。从实验第56天开始,在主组动物(4-NQO)的涂片中检测到非典型细胞(视野内1-2个),Bethesda术语描述为低级别上皮内病变。鳞状上皮旁基底细胞具有非典型大细胞核(比参比大3倍以上),核异核增多,单个细胞内核膜轮廓变化,染色质粗等特征,具有诊断意义。致癌因子长期暴露主组前肠上皮向癌前状态方向形态改变的严重程度明显高于对照组和完整组(p < 0.05)。因此,我们研究了模拟实验动物上消化道上皮诱发癌变条件的有效性,并通过对口腔黏膜进行机械损伤,外加致癌物(4-NQO)进行了验证。这种致癌激发模型将用于女性生殖系统肿瘤过程的下一步研究。
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