Influence of different levels of dietary casein on initiation of male rat liver carcinogenesis with a single dose of aflatoxin B1.
To analyze the influence of different levels of dietary casein on the initiation process, male Wistar rats, pair-fed on isocaloric diets containing 5, 15 or 40% casein were initiated with a single dose of aflatoxin B1, 28 days after the experimental start. From day 4 after initiation and until selection of initiated cells was started, 25 days later, rats were fed the 15% casein diet, providing an identical dietary background during the selection period. Promotion/selection of initiated cells was performed by the combined treatment with 0.02% 2-acetylaminofluorene in the 15% casein diet for 2 weeks and a two-thirds partial hepatectomy (PH) in the middle of this period. The number of enzyme-altered hepatic lesions per rat was shown to increase with increasing content of casein in the diet, both when liver sections were stained for gamma-glutamyltransferase and with immunohistochemical staining for the placental form of glutathione-S-transferase. Non-initiated rats fed the different levels of casein exhibited a very low number of foci. Livers were secured also from non-initiated rats at the same point of time as initiation was performed. Whereas no significant differences in the total microsomal content of cytochrome P450 were observed, a higher microsomal capacity to perform 16 alpha-hydroxylation of 4-androstene-3,17-dione was observed in preparations from rats fed 40% casein, when compared with rats receiving the 5% casein diet. The dietary protein content at the time of initiation did not affect the expression of the c-rasHa, c-myc or c-fos protooncogenes, either at initiation, on day 3, or at PH.
Department of Medical Nutrition, Karolinska Institute, Huddinge University Hospital, Sweden.
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Blanck
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Lindhe
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Porsch Hällström
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Lindeskog
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Gustafsson
D016604:Aflatoxin B1; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002364:Caseins / Q000008:administration & dosage / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D004044:Dietary Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D011519:Proto-Oncogenes / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D039181:Steroid 16-alpha-Hydroxylase; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D002364:Caseins; D004044:Dietary Proteins; D000735:Androstenedione; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase