[Effects of 5-Aza-2'-deoxycytidine on the carcinogenesis of colorectal cancer in mouse and the in vivo expression of p16/CDKN(2) mRNA].
OBJECTIVE
To explore the effects and relationship of specific demethylation agent 5-Aza-2'-deoxycytidine (5-Aza-CdR) on colorectal cancer (CRC) induced by 1, 2-dimethylhydrazine (DMH) in mouse and the in vivo expression of cyclin-dependent kinases inhibitor p16/CDKN(2) mRNA.


METHODS
A total of 40 male KM mice were randomized into 2 groups and CRC was induced by a 22-week injection of DMH. One group was interfered by specific DNA methyltransferase inhibitor 5-Aza-CdR. Another 10 the same source male KM mice were induced by a 22-week injection of saline as none induced cancer control group (negative control group). All mice were sacrificed to examine for colorectal neoplasm. Immunohistochemical staining was used to assess the expression of proliferating cell nuclear antigen (PCNA). The expression of p16/CDKN(2) mRNA was detected by in situ hybridization.


RESULTS
The average numbers of neoplasm was higher in the DMH group (7.6 ± 3.1) than that of the group DMH + 5-Aza-CdR (3.4 ± 1.8, P < 0.05). Immunohistochemical staining showed there was a significant elevation of PCNA in the group DMH (16/19) as compared with that in the group DMH + 5-Aza-CdR (11/19, P < 0.05). In situ hybridization revealed that the level of tumor suppressor gene p16/CDKN(2) mRNA was significantly lower in the group DMH than that in the group DMH + 5-Aza-CdR.


CONCLUSIONS
The specific demethylation agent 5-Aza-2'-deoxycytidine may inhibit the carcinogenesis of CRC. Its mechanism may be related with a high expression of p16/CDKN(2) mRNA.
Department of General Surgery, No.117 Hospital of PLA, Hangzhou 310013, China.
Xiao-Ming
XM
Fang
Zhao-Hui
ZH
Jiang
Ning
N
Yao
Xiao-Wen
XW
Ding
Jia-Ping
JP
Peng
Shu
S
Zheng
D000818:Animals; D000964:Antimetabolites, Antineoplastic; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger