Aberrant crypt foci and colon cancer: comparison between a short- and medium-term bioassay for colon carcinogenesis using dimethylhydrazine in Wistar rats

Abstract

Aberrant crypt foci (ACF) in the colon of carcinogen-treated rodents are considered to be the earliest hallmark of colon carcinogenesis. In the present study the relationship between a short-term (4 weeks) and medium-term (30 weeks) assay was assessed in a model of colon carcinogenesis induced by dimethylhydrazine (DMH) in the rat. Sixweek-old male Wistar rats were given subcutaneous injections of DMH (40 mg/kg) twice a week for 2 weeks and killed at the end of the 4th or 30th week. ACF were scored for number, distribution pattern along the colon and crypt multiplicity in 0.1% methylene-blue wholemount preparations. ACF were distinguished from normal crypts by their larger size and elliptical shape. The incidence, distribution and morphology of colon tumors were recorded. The majority of ACF were present in the middle and distal colon of DMH-treated rats and their number increased with time. By the 4th week, 91.5% ACF were composed of one or two crypts and 8.5% had three or more crypts, while by the 30th week 46.9% ACF had three or more crypts. Thus, a progression of ACF consisting of multiple crypts was observed from the 4th to the 30th week. Nine well-differentiated adenocarcinomas were found in 10 rats by the 30th week. Seven tumors were located in the distal colon and two in the middle colon. No tumor was found in the proximal colon. The present data indicate that induction of ACF by DMH in the short-term (4 weeks) assay was correlated with development of well-differentiated adenocarcinomas in the medium-term (30 weeks) assay.

Evaluation of the antimutagenic and anticarcinogenic effects of inulin in vivo

“…was diluted at the time of use in an aqueous solution of ethylenediaminetetraacetic acid (EDTA) (0.37 mg/mL) and administered to the animals intraperitoneally (ip). Treatment was performed according to the protocol in Rodrigues et al (2002). Briefly, 4 doses of DMH were administered in total, 2 doses each week for 2 weeks.…”

Antimutagenic and anticarcinogenic effects of wheat bran in vivo

“…was diluted at the time of use in an aqueous solution of ethylenediaminetetraacetic acid (EDTA; 0.37 mg/mL) and administered to the animals intraperitoneally (ip). Treatment was performed according to the protocol of Rodrigues et al (2002). Briefly, 4 doses of DMH were administered in total, 2 doses each week for 2 weeks.…”

Fish oil ingestion reduces the number of aberrant crypt foci and adenoma in 1,2-dimethylhydrazine-induced colon cancer in rats

“…During the first 2 weeks of the experiment, all animals were given 4 subcutaneous injections of 40 mg/kg body weight DMH (Sigma, USA), two injections in the 1st week, and two in the 2nd week, on nonconsecutive days (7). DMH was prepared immediately before use, dissolved in 0.9% NaCl containing 1.5% EDTA as vehicle at a final concentration of 10 mg/mL, and final pH was adjusted to 6.5.…”

“…ACF and tumors can be chemically induced by administering chemical carcinogens to experimental animals, among them, 1,2-dimethylhydrazine (DMH) or azoxymethane (5,6). DMH is one of the agents most frequently used in experimental models of colon carcinogenesis in rodents (6,7).…”