Dietary oat lipids-induced novel DNA modifications and suppression of altered hepatic foci formation.
Previous studies have shown that the presence of several hepatic I-compounds, i.e., age-dependent covalent DNA modifications, is related to the presence of a natural ingredient, i.e., oats, in the diet. To demonstrate the biological significance of these novel DNA modifications, the effect of oat lipids on tumor initiation and promotion was examined in a rat liver tumor model. Female Sprague-Dawley rats were treated with a single dose of diethylnitrosamine, a hepatic carcinogen, 24 hours after a 70% partial hepatectomy, then subjected to dietary phenobarbital promotion. Diets containing 10% oat lipids or corn oil were given during the initiation or the promotion stage of the tumorigenesis. At the end of the feeding, hepatic I-compounds were measured by 32P postlabeling, and the number and volume of enzyme-altered hepatic foci, which served as preneoplastic markers, were measured in serial sections of liver by the method of quantitative stereology. Rats receiving oat lipids-supplemented diets had five- to sixfold higher levels of I-compounds in their liver DNA than those receiving control diets. Meanwhile, rats receiving diets containing oat lipids during promotion had significantly smaller numbers and reduced volume of altered hepatic foci compared with those fed the control diet containing corn oil. These observations support the hypothesis that some I-compounds, e.g., the oats-specific I-compounds, are novel DNA modifications related to nutrient metabolism. The diet containing oat lipids may have chemopreventive activities, as demonstrated in this model system.
Li
D
D
Department of Gastrointestinal Oncology and Digestive Diseases, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Wang
M
M
Paul
G P
GP
Pitot
H C
HC
Dragan
Y
Y
D000704:Analysis of Variance; D000818:Animals; D016588:Anticarcinogenic Agents; D018554:Avena; D002273:Carcinogens; D018736:DNA Adducts; D004041:Dietary Fats; D004052:Diethylnitrosamine; D004195:Disease Models, Animal; D005260:Female; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013489:Suppression, Genetic
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D018736:DNA Adducts; D004041:Dietary Fats; D004052:Diethylnitrosamine