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A New Medium-term Rat Colorectal Bioassay Applying Neoplastic Lesions as End Points for Detection of Carcinogenesis Modifiers Effects with Weak or Controversial Modifiers

¹ Division of Pathology, National Institute of Health Sciences, Tokyo 158-8501, Japan
² Food Safety Commission, Tokyo 100-8989, Japan

Correspondence: Address correspondence to: Young-Man Cho, Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-Ku, Tokyo 158-8501, Japan; e-mail:ymcho{at}nihs.go.jp.

We have established a two-stage, medium-term rat colorectal carcinogenesis model featuring induction of neoplastic lesions within ten weeks. In the present study, we examined the ability of this model to detect weak modifiers. F344 male rats were given three subcutaneous (sc) injections of 1,2-dimethyl-hydrazine (DMH, 40 mg/kg b.w.) in one week followed by drinking water containing 1% dextran sodium sulfate (DSS) for a second week. One week after this regimen, basal diet alone, or diets containing 10% perilla oil, 10% corn oil, 10% dextrin, or 0.1% indole-3-carbinol (I3C) were supplied. The perilla oil and corn oil groups did not show significant differences in the numbers of aberrant crypt foci (ACF) and incidences or multiplicity of proliferative lesions as compared to the controls at either time point. In the dextrin group, the total number of ACF at week ten was significantly increased. With I3C, the total number of ACF and incidence and multiplicities of adenocarcinomas at week ten and the incidence of invasive tumors at week twenty were significantly increased. These data essentially correspond with earlier reported results, except in the vegetable oil cases. Thus, the system is suitable for detection of colorectal carcinogenesis modifiers with advantages over previous models using ACF alone as end points.

Key Words: colon • rat • bioassay • 1,2-dimethylhydrazine • dextran sodium sulfate • aberrant crypt foci

Abbreviations: DMH, 1, 2-dimethylhydrazine • DSS, dextran sodium sulfate • ACF, aberrant crypt foci • I3C, indole-3-carbinol • AOM, azoxymethane • MNU, N-methyl-N-nitrosourea

This version was published on April 1, 2008

Toxicologic Pathology, Vol. 36, No. 3, 459-464 (2008)
DOI: 10.1177/0192623308315358


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