MORPHOMETRIC STUDY OF THE RAT DUODENAL EPITHELIUM DURING THE INITIAL 6 MONTHS OF 1,2-DIMETHYLHYDRAZINE CARCINOGENESIS

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (10) , 4838-4849
Abstract
Male Wistar rats weighing 100 g received 1,2-dimethylhydrazine (25 mg/kg) s.c. twice/wk for 2 mo. and once/wk thereafter for an additional 4 mo. Groups of 4-6 rats were sacrificed monthly. Paraffin sections of duodenum were prepared and stained with periodic acid-Schiff and hematoxylin for cell counts and with toluidine blue for measuring nucleolar area. As an index of villus size and crypt size, the mean number of epithelial cells per representative sections of villi and crypts were used. Mitotic activity was assessed by counting the mean number of mitotic figures per representative crypt section. Nucleolar area was assessed from the analysis of drawn (camera lucida) images of nucleoli of columnar cells at 6 levels of the epithelium: lower, mid and upper parts of the crypts and villi. Villus size increased progressively during the 6 mo. treatment, from 272 .+-. 2 (SE) to 349 .+-. 8. Crypt size increased from 118 .+-. 2 in a wavy fashion, showing maximum (139 .+-. 5, 143 .+-. 2) at 3 and 6 mo. and minimum (123 .+-. 3, 127 .+-. 1) at 1 and 4 mo. Mitotic number displayed a similar pattern of increase so that the percentage of mitotic figures in the crypts (mitotic index) remained constant (.apprx. 5%) in control and experimental animals. Nucleolar area in the controls decreased with age from 4.2 .+-. 0.08 sq .mu.m in lower crypt at 1 mo. to 2.8 .+-. 0.04 sq .mu.m at 6 mo. During 1,2-dimethylhydrazine treatment, lower crypt nucleoli increased to 4.5 .+-. 0.12 sq .mu.m after 3 mo. and decreased slightly thereafter, reaching 4.0 .+-. 0.14 sq .mu.m by the 6th mo. The nucleoli furthermore decreased gradually along epithelium (nucleolar compaction) by an average of 0.23% per cell position in control and treated animals. The main effect of 1,2-dimethylhydrazine was the enlarging of the 4 parameters measured. This effect seemed to relate in some manner to tumor formation as all the enlargements were attenuated in intestinal tissue adjacent to tumors.