Effect of disulfiram on 1,2-dimethlhydrazine- and azoxymethane- induced aberrant crypt foci

We have previously reported a method for visualizing the mucosalsurface of fixed unsectioned rodent colons at the crypt leveland have identified lesions, termed aberrant crypt foci (ACF),in the colons of carcinogen-treated rodents. We hypothesizedthat ACF represent the precursor lesions (PL) of colon cancer.In the present study, the effect of feeding disulfiram (DSF)added to a semi-synthetic diet (0.5% or 1% by wt) on 1,2-dimethylhydrazine(DMH) and azoxymethane (AOM) induced ACF was investigated. DSFhas been shown to inhibit DMH and AOM-induced colon cancer.Therefore, it was reasoned that if ACF represent PL then theirinduction and growth should also be inhibited by DSF. CF1 femalemice were randomly divided into three groups of 30 each. Group1 was fed a diet containing 1% DSF for 9 days prior to and 1day after receiving a single i.p. injection of either DMH, AOMor saline. Group 2 was fed a diet containing 1% DSF for 9 daysprior to and 14 days after receiving a single i.p. injectionof DMH, AOM or saline, whereas group 3 received control dietthroughout the experimental duration. All animals were killed5 weeks after receiving the injections. It was observed thatfeeding DSF, for 9 days prior to and for either 1 day or 14days after the administration of a single injection of DMH,resulted in a complete inhibition of ACF. DSF feeding for 9days prior to and 1 day after AOM injection resulted in a significantlygreater number of ACF compared to the control group (12 ? 2.3vs 7.2 ? 1.2); whereas DSF feeding for a longer duration (i.e.9 days prior to and 14 days after AOM treatment) was associatedwith a significantly lower number of ACF compared to those fedDSF for only one day after AOM treatment (4.1 ? 0.6 vs 12.4? 2.3) and a lower number compared to the control group (4.1? 0.6 vs 7.2 ? 1.2).