Effects of Perinatal Exposure to Acrylamide and Glycidamide on Intestinal Tumorigenesis in Min/+ Mice and Their Wild-type Litter Mates

Abstract

The tumorigenic capacity of acrylamide (AA) in the intestine of C57BL/6J Min/+ mice, as well as in their wild-type (wt) litter mates was investigated. In Experiment 1, the mice were s.c. injected with 10 or 50 mg/kg body weight (bw) of AA or glycidamide (GA) at week 1 and 2 after birth. In Experiment 2, the mice were given 50 mg/kg bw/injection of AA or GA 1 week before birth to the dam, alone or in combination with exposure of the pups at week 1 and 2 after birth. Following GA exposure at week 1 and 2, the formation of small intestinal tumors in Min/+ mice increased in a dose-dependent manner (r_s=0.32, p=0.008): a 1.3-fold increase in the number of tumors with 50 mg/kg bw GA compared to the controls (p<0.05). In the wt litter mates, there was a dose response relationship between the GA exposure and the frequency of animals with one or more intestinal neoplasm (intestinal tumors + aberrant crypt foci) (p=0.018): at 50 mg/kg bw of GA an 8-fold induction was found compared to the controls (p=0.017). In Experiment 2, Min/+ mice exposed to GA in utero had fewer small intestinal tumors than the controls (p<0.05). However, following GA exposure the number of intestinal tumors correlated positively with the number of injections (small intestine: r_s=0.32, p=0.002; colon: r_s=0.27, p=0.01). When exposed early in life, GA is a weak intestinal tumorigen in Min/+ mice and their wt litter mates.