Induction of Transplantable Tumors by Repeated Subcutaneous Injections of Natural and Synthetic Vitamin E in Mice and Rats

Abstract

Natural vitamin E and synthetic vitamin E (dl/‐α‐tocopheryl acetate) were tested for their tnmorigenicity in rodents. Transplantable tumors, at the site of injection, were induced by repeated injections of these compounds in two strains of mice, NFS/N and C57BL/6N × C3H/He Fl, and in a strain of rats, Fischer 344. Natural vitamin E was tumorigenic in both strains of female mice only when injected with soya oil. In contrast, dl‐α‐tocopheryl acetate alone was capable of inducing tumors in Fischer 344 rats. Only one out of 5 male NFS/N mice given dl‐α‐tocopheryl acetate developed a tumor. Therefore, Fischer 344 rats were more susceptible to tumor formation by dl‐α‐tocopheryl acetate than NFS/N mice. dl‐α‐Tocopheryl acetate with soya oil or with palm oil also resulted in the formation of transplantable tumors in NFS/N mice and Fischer 344 rats. There was no difference in the tumor incidence between mice treated with dl‐α‐a‐tocopheryl acetate alone and dl‐α‐tocopheryl acetate plus soya oil or palm oil. However, in rats, the incidence was lower for a group treated with dl‐α‐tocopheryl acetate plus palm oil than for those with dl‐αa‐tocopheryl acetate alone and with dl‐α‐tocopheryl acetate plus soya oil.

Gamma-tocopherol detoxification of nitrogen dioxide: superiority to alpha-tocopherol.

“…a-T functions effectively as an inhibitor of lipid peroxidation and inhibits nitrosation when assessed in short-term assays (43,44,55); however, simultaneous formation of a nitrosating agent from reaction with NO2 suggests that long-term protection from genotoxic deamination reactions may be incomplete. This may explain enhanced tumor formation when a-T is administered to animals at high doses (17,18). Nitta et al (18) observed an inflammatory response at the site oftocopherol injection, suggesting that generation of free radicals by invading macrophages may have contributed to tumor formation.…”

“…This may explain enhanced tumor formation when a-T is administered to animals at high doses (17,18). Nitta et al (18) observed an inflammatory response at the site oftocopherol injection, suggesting that generation of free radicals by invading macrophages may have contributed to tumor formation.…”

Tailoring cancer chemoprevention regimens to the individual

“…In additional unpublished studies in our laboratory, topical applications of a-tocopherol 5 days a week to initiated high risk mice previously treated with UVB for 5 months enhanced the formation of skin tumors. In addition, the growth of tumors transplanted into mice, rats, or chickens was stimulated when the animals received multiple injections of vitamin E [Kline and Sanders, 1989;Nitta et al, 1991].…”

Self-Organization of Silver-Core Bimetallic Nanoparticles and Their Application for Catalytic Reaction

“…On the other hand, every antioxidant is in fact, a redox agent, protecting against reactive oxygen species in some circumstances and promoting free radical or secondary reactive oxygen species generation in others. Indeed, an excess of these antioxidants elevates the incidence of cancer (Nitta et al 1991;Omenn et al, 1996). Solovieva et al reported that antioxidants, ascorbic acid (Solovieva et al, 2007) and dithiothreitol (Solovieva et al, 2008), exhibit cytotoxicity via H 2 O 2 generation.…”

“…(Yamashita et al, 1998;Murata & Kawanishi, 2000). Indeed, an excess of these antioxidants elevates the incidence of cancer (Nitta et al, 1991;Omenn et al, 1996). A catalyst consisting of an inorganic stable material is not oxidized and does not generate secondary reactive oxygen species.…”