Frequency of proliferation, apoptosis, and their ratio during rat colon carcinogenesis and their characteristic pattern in the dimethylhydrazine-induced colon adenoma and carcinoma.
The imbalance between the cell proliferation and cell loss plays a crucial role in the carcinogenesis and tumor progression. However, the direction of these changes is still the matter of discussion. Thus, the aim of this study was to evaluate the proliferative activity, apoptotic activity, and proliferation/apoptosis ratio (P/A) assessed every 6 weeks in the colonic epithelium during 21 weeks of dimethylhydrazine (DMH) treatment in male Wistar rats. Moreover, it is necessary to answer the question whether these analyzed parameters correlate with the grade of differentiation or dysplasia of the induced tumors. It was found that DMH administration enhanced the proliferation in week 12 and 18 when compared with week 6. The proliferation in the control group did not change during the study. Up to week 12 of the experiment, there were no statistically significant differences between proliferative activity in the control and DMH-treated groups. In week 18, the proliferation in DMH-treated group was higher than in the control group. At all time points of the study, the apoptotic activity in the DMH-treated groups was significantly higher than in controls and in both groups, they dropped during the study. In the control group, apoptotic activity decreased in week 18 and was lower in comparison to that in week 6 and 12. In the group treated with DMH, apoptosis dropped at week 12 and was lower than in week 6. The P/A ratio did not change during the study in the control group, but increased in the DMH-treated group. After 21 weeks of DMH administration, 28 cases of colon adenocarcinoma and nine cases of colon adenoma were obtained and classified according to the WHO classification (1989) for human colon tumors. The adenocarcinomas were divided into four groups: well, moderately, poorly differentiated, and signet-ring cell carcinoma. The colon adenomas were divided into three groups: adenoma with mild, moderate, and severe grade of dysplasia. The proliferative activity in signet-ring cell carcinoma was significantly smaller than in well, moderately, and poorly differentiated adenocarcinoma and apoptotic activity was smaller than in well-differentiated adenocarcinoma. A weak (statistically nonsignificant) negative correlation was also observed between the proliferative and apoptotic activity in adenocarcinoma or adenoma and their grade of dedifferentiation or dysplasia, respectively.
Department of Experimental Endocrinology and Hormone Diagnostics, Institute of Endocrinology, Medical University of Łódź, Dr. Sterling Str. 3, 91-425 Łódź, Poland.
Gabriela
G
Mełeń-Mucha
Hanna
H
Niewiadomska
D000236:Adenoma / Q000139:chemically induced / Q000503:physiopathology* / Q000662:veterinary; D000818:Animals; D017209:Apoptosis; D002273:Carcinogens / Q000008:administration & dosage / Q000009:adverse effects*; D002277:Carcinoma / Q000139:chemically induced / Q000503:physiopathology* / Q000662:veterinary; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000503:physiopathology* / Q000662:veterinary; D004127:Dimethylhydrazines / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D004127:Dimethylhydrazines