Rapid induction of colorectal tumors in rats initiated with 1,2-dimethylhydrazine followed by dextran sodium sulfate treatment.
To establish a rapid bioassay system with neoplastic end-points for detection of colorectal carcinogenesis modifiers, we evaluated the effects of dextran sodium sulfate (DSS) treatment on the different stages of carcinogenesis in rats initiated with 1,2-dimethylhydrazine (DMH). F344 male rats were given three subcutaneous injections of DMH (40 mg/kg body weight) in a week, and were administered drinking water containing 1.0% DSS ad libitum either during or after the initiation period for a week, or both during and after initiation periods for 2 weeks. At the 10th week of the experiment, although the numbers of aberrant crypt foci were significantly decreased in all groups treated with DSS and given DMH-initiation as compared with DMH alone, dysplastic foci/adenomas/adenocarcinomas were increased. The incidences and multiplicities of these lesions were highest in rats treated with DSS after DMH-initiation period. At the 26th week, the incidences of adenocarcinomas (100 vs. 20% in DMH alone) and their multiplicities (6.6 +/- 0.8/rat vs. 0.2 +/- 0.4/rat in DMH alone) were also highest in this group. These results indicate that short-term DSS-treatment in the post-initiation period significantly accelerates DMH-induced colorectal tumor development in rats, so that this protocol may effective for establishment of a rapid bioassay system with neoplastic end-points.
Onose
Jun-ichi
J
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Imai
Toshio
T
Hasumura
Mai
M
Ueda
Makoto
M
Hirose
Masao
M
D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology*; D009367:Neoplasm Staging; D051381:Rats
D002273:Carcinogens; D016264:Dextran Sulfate; D019813:1,2-Dimethylhydrazine