Expression of metallothionein in dimethylhydrazine-induced colonic precancerous and cancerous model in rat.
OBJECTIVE
Metallothionein (MT) is a small protein with a high affinity for divalent heavy metals and has a function in zinc homeostasis. The purpose of this study was to assess the MT mRNA gene expression as well as the MT protein content by immunohistochemistry and radioimmunoassay (RIA) in 1,2-dimethylhydrazine (DMH)-induced precancerous and cancerous colonic tissue in rats.


METHODS
Six-week-old rats were given subcutaneous injections of DMH twice a week for 3 months and sacrificed at 4 months (precancerous model) and 6 months (cancerous model). We determined MT mRNA expression by reverse transcription polymerase chain reaction and MT protein content by both immunohistochemical expression and cadmium-109 RIA.


RESULTS
MT mRNA expression in the large intestine showed statistically significant decrease in the precancerous (P < 0.01) and the cancerous (P < 0.001) model as compared with controls. Immunohistochemical expression of MT showed statistically significant decrease (P < 0.05) in the colonic cancerous tissue. MT content in the large intestine showed statistically significant decrease in precancerous (P < 0.005) and cancerous (P < 0.001) model as compared with controls.


CONCLUSIONS
This study suggests that a decrease in the colonic MT mRNA expression, MT protein expression, and content in DMH-induced colonic cancer model is associated with the development of preneoplastic lesions and further progression to carcinoma in the colon results in a greater reduction in the levels of each of these parameters.
Department of Clinical Biochemistry, Christian Medical College, Vellore, Tamil Nadu, India.
Pamela
P
Christudoss
Department of Neuropathology, Christian Medical College, Vellore, Tamil Nadu, India.
Geeta
G
Chacko
Department of Clinical Biochemistry, Christian Medical College, Vellore, Tamil Nadu, India.
Ratnasamy
R
Selvakumar
Department of Clinical Biochemistry, Christian Medical College, Vellore, Tamil Nadu, India.
Jude Joseph
JJ
Fleming
Department of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India.
Srinivasan
S
Pugazhendhi
Department of General Surgery, Christian Medical College, Vellore, Tamil Nadu, India.
George
G
Mathew
D019813:1,2-Dimethylhydrazine / Q000009:adverse effects; D000818:Animals; D003110:Colonic Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D007150:Immunohistochemistry; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D011230:Precancerous Conditions; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D012333:RNA, Messenger; D008668:Metallothionein; D019813:1,2-Dimethylhydrazine