1.Pathogenic and tumorigenic effect of 1,2-dimethylhydrazine in mouse colon and ovarian.
Xin LI ; Li-Na YU ; Qing-Ling ZHANG ; Lu QI ; Yan-Qing DING
Journal of Southern Medical University 2011;31(6):999-1002
OBJECTIVETo study the pathogenic and tumorigenic effect of 1,2-dimethylhydrazine (DMH) on the colon and ovaries of mice.
METHODSSixty ICR female mice were randomly divided into groups A and B for intraperitoneal injection of DMH (20 mg/kg) and saline (control) once a week for 24 weeks, respectively. The mice were sacrificed at 12, 16, 20, 24, 28 and 32 weeks after the first DMH injection for pathological examination of the colon and ovaries.
RESULTSIn group A, colorectal adenomas were found in 7, colorectal adenocarcinomas in 5, and hemorrhagic lesions of the ovaries with chronic inflammatory in 21 mice. Choriocarcinoma in the ovaries were detected in one mouse at 28 weeks and in another at 32 weeks. No obvious pathological changes were found in group B following the injections.
CONCLUSIONIntraperitoneal injection of DMH may induce colon tumors and ovarian diseases in mice.
1,2-Dimethylhydrazine ; toxicity ; Animals ; Colon ; drug effects ; pathology ; Colonic Neoplasms ; chemically induced ; Female ; Mice ; Mice, Inbred ICR ; Ovarian Diseases ; chemically induced ; Ovary ; drug effects ; pathology
2.Preventive effects of berberine on experimental colon cancer and relationship with cyclooxygenase-2 expression.
Ke WU ; Junxia YANG ; Qixin ZHOU
China Journal of Chinese Materia Medica 2010;35(20):2768-2773
OBJECTIVETo investigate the anti-colon cancer effects of berberine and possible relationship with cyclooxygenase-2.
METHODWistar rat colon cancer model was induced by 1-2 dimethylhydrazine (DMH) (40 mg x kg(-1), sc) + 1% dextran sodium sulfate solution (DSS) (freely drinking). All rats were randomly divided into 3 groups: Control (DMH + DSS + solvant), meloxicam (Mel) (DMH + DSS + Mel 1.35 mg x kg(-1)), berberine (Ber) (DMH + DSS + Ber 100 mg x kg(-1)). The drugs were given orally once a day for 5 day per week. The body weight, the number of colon ACFs, the incidence and number of colon cancer in rats, as well as the morphological changes of rat colon tissues were evaluated. Human colon cancer lovo cell line was treated by either Ber or Mel in various concentrations (1 10(-6) mol x L(-1), 1 x 10(-5) mol x L(-1), 1 x 10(-4) mol x L(-1), 1 x 10(-3) mol x L(-1)) for 6, 12 and 24 h, respectively, and the cell growth was assayed by MTT method. RT-PCR and western-blot were used to evaluate the mRNA and protein expressions of COX-2 from lovo cells treated with Ber and Mel.
RESULTBer significantly improved the dyscrasia induced by DMH + DSS, the both of body weight and general condition were better than control group. Ber also significantly inhibited ACF and colon cancer incidence in the rats treated by DMH + DSS for 10 weeks or 20 weeks, which was similar to that of Mel. Ber inhibited the proliferation of lovo cells in concentration- and time-dependent manners, and the IC50 values were significantly smaller than that of Mel at 6, 12 and 24 h after lovo cells were treated by either Ber or Mel. Ber also concentration-dependently decreased expressions of COX-2 mRNA and COX-2 protein from lovo cells.
CONCLUSIONBer can inhibit ACF and tumor formation induced by DMH + DSS, and decrease the lovo cell proliferation index. The anti-tumor effects of Ber may involve in an unknown pathway through which the expressions of COX-2 mRNA and protein were inhibited.
1,2-Dimethylhydrazine ; toxicity ; Aberrant Crypt Foci ; prevention & control ; Animals ; Berberine ; therapeutic use ; Body Weight ; drug effects ; Colonic Neoplasms ; enzymology ; prevention & control ; Cyclooxygenase 2 ; genetics ; Dextran Sulfate ; toxicity ; Female ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar
3.Overexpression of cyclin D1 and cyclin E in 1,2-dimethylhydrazine dihydrochloride-induced rat colon carcinogenesis.
Kwon HUR ; Jung Rae KIM ; Byung Il YOON ; Jung Keun LEE ; Jae Hoon CHOI ; Goo Taeg OH ; Dae Yong KIM
Journal of Veterinary Science 2000;1(2):121-126
Deregulation of G1 cyclins has been reported in several human and rodent tumors including colon cancer. To investigate the expression pattern of G1 cyclins in 1,2- dimethyl-hydrazine dihydrochloride (DMH)-induced rat colon carcinogenesis, we studied the expression of cyclin D1 and cyclin E by quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis and immunohistochemistry (IHC). The mRNA level of cyclin D1 was increased 1.2-fold in adenocarcinomas but not significantly in adenomas, when compared with normal rat colonic mucosa (p<0.05). The cyclin E mRNA level was increased 2.7-fold in adenomas and 3.3-fold in adenocarcinomas (p<0.05). The PCNA mRNA level was also increased 1.9-fold in adenomas and 1.8-fold in adenocarcinomas (p<0.05). Immunohistochemical staining revealed exclusive nuclear staining of the neoplastic cells for cyclin D1, cyclin E and PCNA. Cyclin D1 expression was detected in 56.3% of the adenomas and in 61.5% of the adenocarcinomas examined, whereas cyclin E expression was detected in 87.5% of the adenomas and in 92.3% of the adenocarcinomas. Overall, cyclin D1, cyclin E and PCNA expression was significantly increased at both the mRNA and protein levels in normal colonic mucosa, adenomas and adenocarcinomas, but there was no significant difference in the degree of expression of these genes in adenomas and adenocarcinomas. Our results indicate that the overexpression of cyclin D1 and cyclin E may play an important role during the multistage process of rat colon carcinogenesis, at a relatively early stage, and may disturb cell-cycle control in benign adenomas, and thereafter, participate in tumor progression.
1,2-Dimethylhydrazine/toxicity
;
Adenocarcinoma/*chemically induced/metabolism
;
Adenoma/*chemically induced/metabolism
;
Animals
;
Carcinogens/toxicity
;
Cell Cycle/drug effects/physiology
;
Colon/metabolism
;
Colonic Neoplasms/*chemically induced/metabolism
;
Cyclin D1/*biosynthesis/genetics
;
Cyclin E/*biosynthesis/genetics
;
Gene Expression Regulation, Neoplastic
;
Immunohistochemistry
;
Male
;
Proliferating Cell Nuclear Antigen/biosynthesis/genetics
;
RNA, Messenger/metabolism
;
Rats
;
Rats, Sprague-Dawley
;
Reverse Transcriptase Polymerase Chain Reaction