Effects of a high fat diet on liver DNA methylation in rats exposed to N-nitrosodimethylamine.
Previous experiments have shown that a high fat diet changes incidence and tumour sites by N-nitroso-dialkylamines. The purpose of this study was to examine the effect of high and low fat diet on DNA methylation 6 weeks after the end of a chronic N-nitrosodimethylamine (NDMA) exposure (total dose 150 mg/kg). The concentration of O6-methyldeoxyguanosine (O6-MedG) in liver DNA was measured by immunoassays. The level of O6-MedG persisted 6 weeks after the last dose of NDMA and was 6-fold higher (P less than 0.05) in animals on high fat as compared to low fat diet. In another experiment, in which rats on a low and high fat diet received a single NDMA dose (2 mg/kg), the time-dependent removal of O6-MedG from liver and the hepatic O6-methylguanine DNA-alkyltransferase activity was not modified by the type of diet. These results indicate that a high fat diet enhances DNA methylation in the liver, after chronic treatment by NDMA, and that this effect is likely to be responsible for an increased incidence of liver haemangiosarcomas.
Camus
A M
AM
International Agency for Research on Cancer, Lyon, France.
Béréziat
J C
JC
Shuker
D E
DE
Hietanen
E
E
Wild
C P
CP
Montesano
R
R
Bartsch
H
H
D000818:Animals; D004247:DNA / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004041:Dietary Fats / Q000009:adverse effects*; D004128:Dimethylnitrosamine / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects*; D008297:Male; D008745:Methylation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D004041:Dietary Fats; D004247:DNA; C015558:O(6)-methyl-2'-deoxyguanosine; D003849:Deoxyguanosine; D004128:Dimethylnitrosamine