Depletion of colonic detoxication enzyme activity in mice with dextran sulphate sodium-induced colitis.
BACKGROUND
The increased risk of colonic malignancies in individuals with ulcerative colitis has prompted a search for early biomarkers of disease progression.


OBJECTIVE
To characterize Phase II detoxication enzyme expression during acute and chronic colitis. The mouse model of dextran sulphate sodium (DSS)-induced colitis represents a relevant system with which to sequentially evaluate the spectrum of biochemical changes associated with colorectal cancer risk.


METHODS
Acute and chronic colitis were induced in Swiss Webster mice by administering DSS in the drinking water (5%) for 1-4 cycles. Each cycle consisted of 7 days DSS and 14 days of water. The glutathione S-transferase (GST) activity, gamma-glutamylcysteine synthetase (gamma-GCS) activity and glutathione content of the colonic tissues were determined at various time points throughout the experiment. Alterations in GST isozyme expression were confirmed by Western and Northern blot.


RESULTS
GST activity was reduced significantly in the colon by the end of Cycle 1 (84% of control values). Specific activities continued to decrease with subsequent cycles of DSS exposure. By the end of Cycle 4, glutathione levels and gamma-GCS activity had reached 29% and 56% of control, respectively.


CONCLUSIONS
These data suggest that detoxication enzyme depletion is associated with both acute and chronic colitis and may be an important event in the progression of ulcerative colitis to colon cancer.
Clapper
M L
ML
Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA, USA. ml_clapper@fcc.edu
Adrian
R H
RH
Pfeiffer
G R
GR
Kido
K
K
Everley
L
L
Cooper
H S
HS
Murthy
S
S
D000818:Animals; D015415:Biomarkers; D015152:Blotting, Northern; D015153:Blotting, Western; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology*; D003106:Colon / Q000201:enzymology*; D003110:Colonic Neoplasms / Q000201:enzymology; D016264:Dextran Sulfate; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice
D015415:Biomarkers; D007527:Isoenzymes; D016264:Dextran Sulfate; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione