Hepatocellular carcinomas are promoted by tocopheryl acetate but eliminated by tocopheryl succinate

Background: The major causes of hepatocellular carcinomas are Aflatoxin, hepatitis B and hepatitis C viruses.Alpha tocopherol and its acetate and succinate esters have each been reported as counteracting cancer development in humans and rodents. We have investigated their salutary effect in both poo...

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Main Authors: Bryant L. Adams, Richard O. Whitten
Format: Article
Language:English
Published: Elsevier 2018-09-01
Series:Journal of Nutrition & Intermediary Metabolism
Online Access:http://www.sciencedirect.com/science/article/pii/S2352385917302621
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author Bryant L. Adams
Richard O. Whitten
author_facet Bryant L. Adams
Richard O. Whitten
author_sort Bryant L. Adams
collection DOAJ
description Background: The major causes of hepatocellular carcinomas are Aflatoxin, hepatitis B and hepatitis C viruses.Alpha tocopherol and its acetate and succinate esters have each been reported as counteracting cancer development in humans and rodents. We have investigated their salutary effect in both poor and high quality diets in rainbow trout Oncorhynchus mykiss as a model. Methods: Hepatocellular carcinomas (HCCs) were induced in rainbow trout by dietary aflatoxin B1 (AfB1). A matrix of different levels of several vitamins and vitamin analogues were included in selected diets as possible anticancer agents. Identification of HCCs was made by histopathology. Results: 1.) Elevated dietary tocopheryl acetate (E-Ac) caused a marked increase in liver size and in AfB1-induced HCCs in rainbow trout. 2.) Poor diets increased the HCC incidence. 3.) Elevated dietary tocopheryl succinate (E-Su) nearly eliminated HCC development in fish fed complete diets. Tocopheryl succinate in poor diets reduced HCCs by 77% compared to tocopheryl acetate diets. 4.) Trans-retinoic acid also reduced HCC incidence. 5.) Vitamins A and D deficiency caused tumor increases but had no effect on liver size. 6.) The use of casein and dextrin in the place of soybean textured vegetable protein, in poor diets nearly eliminated the HCC risk. 7.) Trout sera showed all three vitamin forms; free α-tocopherol (E-OH), tocopheryl acetate (E-Ac) and tocopheryl succinate (E-Su), from diets containing any of these vitamin analogues, suggesting both de-esterification and trans-esterification. 8.) E-Su is discussed in the light of an anti-cancer agent that is non toxic to normal tissue but that cohorts to it are needed. Conclusions: Increased dietary E-Ac escalated AfB1 induced HCCs and caused hepatomegaly in rainbow trout, while E-Su eliminated the HCC risk as shown by histopathology. Keywords: Aflatoxin, Tocopheryl-acetate, Tocopheryl-succinate, Hepatocellular, carcinomas, Hepatomegaly
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spelling doaj.art-a1d75e1855cc47a29ff44f53ba8a2d7b2022-12-21T19:00:26ZengElsevierJournal of Nutrition & Intermediary Metabolism2352-38592018-09-01133347Hepatocellular carcinomas are promoted by tocopheryl acetate but eliminated by tocopheryl succinateBryant L. Adams0Richard O. Whitten1Health Environment Analysis Laboratory, 2343 63rd CT, SW, Tumwater, WA, USA; Corresponding author.Cellnetix Pathology Laboratory, Olympia, WA, 98506, USABackground: The major causes of hepatocellular carcinomas are Aflatoxin, hepatitis B and hepatitis C viruses.Alpha tocopherol and its acetate and succinate esters have each been reported as counteracting cancer development in humans and rodents. We have investigated their salutary effect in both poor and high quality diets in rainbow trout Oncorhynchus mykiss as a model. Methods: Hepatocellular carcinomas (HCCs) were induced in rainbow trout by dietary aflatoxin B1 (AfB1). A matrix of different levels of several vitamins and vitamin analogues were included in selected diets as possible anticancer agents. Identification of HCCs was made by histopathology. Results: 1.) Elevated dietary tocopheryl acetate (E-Ac) caused a marked increase in liver size and in AfB1-induced HCCs in rainbow trout. 2.) Poor diets increased the HCC incidence. 3.) Elevated dietary tocopheryl succinate (E-Su) nearly eliminated HCC development in fish fed complete diets. Tocopheryl succinate in poor diets reduced HCCs by 77% compared to tocopheryl acetate diets. 4.) Trans-retinoic acid also reduced HCC incidence. 5.) Vitamins A and D deficiency caused tumor increases but had no effect on liver size. 6.) The use of casein and dextrin in the place of soybean textured vegetable protein, in poor diets nearly eliminated the HCC risk. 7.) Trout sera showed all three vitamin forms; free α-tocopherol (E-OH), tocopheryl acetate (E-Ac) and tocopheryl succinate (E-Su), from diets containing any of these vitamin analogues, suggesting both de-esterification and trans-esterification. 8.) E-Su is discussed in the light of an anti-cancer agent that is non toxic to normal tissue but that cohorts to it are needed. Conclusions: Increased dietary E-Ac escalated AfB1 induced HCCs and caused hepatomegaly in rainbow trout, while E-Su eliminated the HCC risk as shown by histopathology. Keywords: Aflatoxin, Tocopheryl-acetate, Tocopheryl-succinate, Hepatocellular, carcinomas, Hepatomegalyhttp://www.sciencedirect.com/science/article/pii/S2352385917302621
spellingShingle Bryant L. Adams
Richard O. Whitten
Hepatocellular carcinomas are promoted by tocopheryl acetate but eliminated by tocopheryl succinate
Journal of Nutrition & Intermediary Metabolism
title Hepatocellular carcinomas are promoted by tocopheryl acetate but eliminated by tocopheryl succinate
title_full Hepatocellular carcinomas are promoted by tocopheryl acetate but eliminated by tocopheryl succinate
title_fullStr Hepatocellular carcinomas are promoted by tocopheryl acetate but eliminated by tocopheryl succinate
title_full_unstemmed Hepatocellular carcinomas are promoted by tocopheryl acetate but eliminated by tocopheryl succinate
title_short Hepatocellular carcinomas are promoted by tocopheryl acetate but eliminated by tocopheryl succinate
title_sort hepatocellular carcinomas are promoted by tocopheryl acetate but eliminated by tocopheryl succinate
url http://www.sciencedirect.com/science/article/pii/S2352385917302621
work_keys_str_mv AT bryantladams hepatocellularcarcinomasarepromotedbytocopherylacetatebuteliminatedbytocopherylsuccinate
AT richardowhitten hepatocellularcarcinomasarepromotedbytocopherylacetatebuteliminatedbytocopherylsuccinate