A rapid dual organ rat carcinogenesis bioassay for evaluating the chemoprevention of breast and colon cancer.
In this study we evaluated the effect of dietary administration of a high fat, low fiber diet (HRD) with or without 2% phytic acid (PA) on the development of mammary cancer and/or colon cancer in rats exposed to methylnitrosourea (MNU), azoxymethane (AOM) or MNU + AOM. The rats were fed a HRD alone or a HRD + 2% PA. At the end of week 2, the rats were given either a s.c. injection of MNU (50 mg/kg body wt) or one of normal saline (vehicle). At the end of weeks 3 and 4, the rats were given either a s.c. injection of AOM (15 mg/kg body wt per week) or one of normal saline (vehicle). Nine weeks after the injection of MNU or saline, 10 rats from each group were sacrificed and the mammary tumor incidence and the number of colonic aberrant crypt foci (ACF) were compared between different groups. The administration of different diets was continued for an additional 21 weeks and the mammary tumor and colon tumor incidence between different groups were compared. Results showed that rats injected with MNU alone did not develop ACF or colon tumors while those injected with AOM alone did not develop mammary tumors. Linear regression analysis of the number of ACF at 11 weeks versus colonic tumor incidence at 32 weeks, and the linear regression analysis of mammary tumor incidence at 11 weeks versus mammary tumor incidence at 32 weeks, both showed good linear correlation. These results demonstrate the potential value of the short term dual organ carcinogenesis bioassay for screening chemopreventive agents for their relative ability to inhibit the development of mammary cancer and/or colon cancer while on high risk diet.
Shivapurkar
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N
Institute for Disease Prevention, George Washington University Medical Center, Washington, DC 20037, USA.
Tang
Z C
ZC
Frost
A
A
Alabaster
O
O
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001397:Azoxymethane; D001943:Breast Neoplasms / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D015197:Carcinogenicity Tests; D002273:Carcinogens; D003043:Cocarcinogenesis; D003110:Colonic Neoplasms / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D004041:Dietary Fats / Q000009:adverse effects; D004043:Dietary Fiber / Q000009:adverse effects; D004354:Drug Screening Assays, Antitumor; D005069:Evaluation Studies as Topic; D005260:Female; D008770:Methylnitrosourea; D010833:Phytic Acid / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004041:Dietary Fats; D004043:Dietary Fiber; D008770:Methylnitrosourea; D010833:Phytic Acid; D001397:Azoxymethane