ASPIRIN, AGE, AND PROXIMITY TO LYMPHOID NODULES INFLUENCE CELL-PROLIFERATION PARAMETERS IN RAT COLONIC CRYPTS

Recent epidemiological studies have demonstrated a correlation between regular aspirin (acetylsalicylic acid) use and decrease risk for the development of fatal colorectal cancer. An increase in the size of the cell proliferation compartment in colorectal crypts has been correlat ed with an increased risk for the development of colon cancer in anima ls and in humans. To determine if acetylsalicylic acid acts to decreas e the size of the cell proliferation compartment, young (3 month) and old (22 month) rats were treated intragastrically with: 1 the vehicle for acetylsalicylic acid delivery (0.25% wt/vol carboxymethylcellulose in 0.15 N HCl), 2 a single dose of acetylsalicylic acid (100 mg/kg), or 3 acetylsalicylic acid (30 mg/kg) given daily for 30 days. One day after the last treatment, colons were resected, fixed, sectioned and m ounted on slides for immunohistochemical staining with a monoclonal an tibody to proliferating cell nuclear antigen to assess cell proliferat ion parameters in the colonic crypts. The results were subjected to th ree way analysis of variance to assess the effects of: 1 rat age, 2 ac ute or chronic acetylsalicylic acid treatment, and 3 location of crypt s over and away from aggregates of lymphoid nodules on the crypt proli ferative parameters. Results demonstrated that: 1 acetylsalicylic acid treatment caused an overall decrease in the proliferative zone height , as measured in number of cells in the crypt column, 2 that crypts lo cated over aggregates of lymphoid nodules had significantly higher pro liferative activity than crypts located away from aggregates of lympho id nodules, and 3 after chronic acetylsalicylic acid treatment there w as a greater suppression of proliferative zone height in the crypts of old rats than in the crypts of young rats. In conclusion, acute and c hronic intragastric delivery of acetylsalicylic acid caused an overall downward shift in the cell proliferation compartment of colonic crypt s of young and of old rats. Whether or not acetylsalicylic acid admini stration will cause the same proliferative zone height response in car cinogen-treated rats is not yet established.