Role of antioxidants on the stimulation of the mitogenic response

By comparing the activities of tocopherol with other antioxidants and tocopherol analogs on mitogenesis of murine spleen cells, an attempt was made to understand the mechanism of tocopherol stimulation. N,N'-diphenyl-p-phenylene diamine (DPPD) was very active in this system, whereas butylated hydroxytoluene, another antioxidant, was much less active. Trolox C, an analog of alpha-tocopherol with a carboxyl group instead of the isoprene side chain was totally inactive. Tocopherol quinone, an oxidized form of tocopherol, was almost as active as tocopherol. Menadione (vitamin K-3), a quinone without a side chain, was also active. It was suggested therefore, that although in tocopherol-like compounds the side chain seems important, the activities of DPPD and menadione clearly do not require it. On the other hand, the stimulation by tocopherol quinone and menadione appears to rule out a requirement for an antioxidant function in mitogenic stimulation. A comparison of the action of tocopherol with indomethacin ruled out regulation of the peroxidation step leading to prostaglandin synthesis as the mechanism for the tocopherol effect.