Sucrose and IQ induced mutations in rat colon by independent mechanism

Sucrose-rich diets have repeatedly been observed to have co-carcinogenic actions in colon and liver of rats and to increase the number of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) induced aberrant crypt foci in rat colon. To investigate a possible interaction between sucrose and IQ on the genotoxicity in rat liver and colon, we gave Big Blue rats a diet containing sucrose (0%, 3.45% or 13.4% w/w) and/or IQ (70 ppm) for a period of 3 weeks. Sucrose and IQ increased the mutation frequency in the colon. The effect of combined treatments with IQ and sucrose on the mutation frequencies was additive indicating that sucrose and IQ act independently. This was supported by the mutation spectra where sucrose expands the background mutations in the colon, whereas IQ, in other studies, more specifically has induced G:C --> T:A transversions. In the liver IQ increased the mutation frequency, whereas addition of sucrose reduced the effect of IQ in a dose-dependent manner. The level of bulky DNA adducts in liver and colon was increased in animals exposed to either sucrose or IQ. In animals exposed to IQ, addition of sucrose had marginal effects on the level of bulky DNA adducts. Markers of oxidative damage and DNA repair were generally unaffected by the treatments. In conclusion, sucrose and IQ in the diet induced mutations in the colon by independent mechanisms, whereas an interaction was observed in liver leading to a decrease in mutations by the combined treatment.