Effects of human diets on biotransformation enzyme activity and metabolic activation of carcinogens in rat liver.
We studied the effects of a complete human diet, based on mean consumption figures in The Netherlands, the heating of food, and the presence of vegetables and fruit in the diet on the drug metabolizing capacity of the rat liver and on metabolic activation of known carcinogens. Groups of five male and five female Wistar rats were given ad lib. one of six different diets for 3 months. Each diet contained 40 energy (E)% fat, 13 E% protein, 47 E% carbohydrate and 5% fibre (w/w). The diets were as follows: a control diet of semi-synthetic materials (A); a human diet of meat, bread and eggs without processing (B); diet B heated under usual household conditions (C); a diet representing a complete human meal including (summer) vegetables and fruit (D); diets consisting of winter vegetables (E) or summer vegetables (F) with fruit. Semi-synthetic components were added to diets B-F to achieve the desired composition. There were differences between male and female rats on the effects of the different diets on hepatic enzyme activity. In female rats, but not in males, ethoxyresorufin-O-deethylase activity was increased significantly (P less than 0.05) in groups C, D and E in comparison with the controls (group A). In male rats ethoxycoumarin-O-deethylase activity was enhanced in groups D, E and F, and glutathione-S-transferase was markedly induced in group F (P less than 0.01). In males, hepatic cytochrome P-450 was significantly (P less than 0.05) increased in groups B, C and E. There was no effect on aminopyrine-N-demethylase activity and almost no effect on UDP-glucuronyltransferase activity in either sex. Microsomes from rats fed heated food (C) markedly increased the mutagenicity of benzo[a]pyrene (B[a]P) in the Ames assay using Salmonella typhimurium strain TA98, in comparison with levels using microsomes from rats fed the raw food (B). Vegetables and fruit decreased B[a]P mutagenicity. All human diets except D decreased the mutagenicity of N-nitrosodimethylamine in tester strain TA100. The results indicate that the influence of components of human diets on rat-liver drug metabolism may have quite different effects on the biotransformation of carcinogens activated by different metabolic pathways.
Alink
G M
GM
Department of Toxicology, Agricultural University, Wageningen, The Netherlands.
Reijven
P L
PL
Sijtsma
S R
SR
Jongen
W M
WM
Topp
R J
RJ
Kuiper
H A
HA
Koeman
J H
JH
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D004032:Diet; D004128:Dimethylnitrosamine / Q000378:metabolism; D005260:Female; D008099:Liver / Q000378:metabolism*; D008297:Male; D010599:Pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
D002273:Carcinogens; D001564:Benzo(a)pyrene; D004128:Dimethylnitrosamine