Dietary low-dose sucrose modulation of IQ-induced genotoxicity in the colon and liver of Big Blue rats.
Earlier studies have indicated that sucrose increases 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced aberrant crypt foci in the colon. In this study, we investigated the role of sucrose in IQ-induced genotoxicity of the colon mucosa and liver. Big Blue rats were fed with IQ (20 ppm in feed) and/or sucrose (3.45 or 6.85 wt.% in feed) for 3 weeks. IQ increased DNA strand breaks in the colon, whereas the mutation frequency was increased in the liver. The level of IQ-induced DNA adducts was elevated in both colon mucosa cells and liver. In the liver, high sucrose intake increased the level of DNA adducts above that of IQ and low sucrose intake. Oxidative DNA damage detected in terms of 7-hydro-8-oxo-2'-deoxyguanosine by HPLC-EC, or endonuclease III or formamidopyrimidine DNA glycosylase sensitive sites were unaltered in the colon and liver. Expression of ERCC1 and OGG1 mRNA levels were unaffected by IQ or sucrose feeding. Biomarkers of oxidative stress, including Vitamin C, malondialdehyde and protein oxidations (gamma-glutamyl semialdehyde and 2-amino adipic semialdehyde) were unaltered in plasma and in liver. In conclusion, sucrose feeding increases IQ-induced genotoxicity in liver but not in colon, suggesting different mechanisms for sucrose and IQ in colon mutagenesis.
Møller
Peter
P
Institute of Public Health, Department of Pharmacology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. fipm@farmakol.ku.dk
Hansen
Max
M
Autrup
Herman
H
Bornholt
Jette
J
Vogel
Ulla
U
Mølck
Anne-Marie
AM
Wallin
Håkan
H
Dragsted
Lars O
LO
Risom
Lotte
L
Poulsen
Henrik E
HE
Loft
Steffen
S
D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor; D002455:Cell Division; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D018736:DNA Adducts / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D019422:Dietary Sucrose / Q000008:administration & dosage / Q000378:metabolism*; D005526:Food, Formulated; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011922:Rats, Mutant Strains; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000633:toxicity*
D014408:Biomarkers, Tumor; D018736:DNA Adducts; D019422:Dietary Sucrose; D009153:Mutagens; C040994:valinol; D014633:Valine