Effects of perinatal exposure to acrylamide and glycidamide on intestinal tumorigenesis in Min/+ mice and their wild-type litter mates.
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.
Olstørn
Hege Benedikte Asvald
HB
Department of Food Safety and Nutrition, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway.
Paulsen
Jan Erik
JE
Alexander
Jan
J
D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000633:toxicity*; D005260:Female; D007414:Intestinal Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology
D004852:Epoxy Compounds; D020106:Acrylamide; C071834:glycidamide