The influence of selenium and neuroleptics on the rat brain nuclear regulatory mechanism in carcinogenesis.

The potential clinical benefit of the antitumor effect of selenium (Se) has recently been confirmed in tumor-bearing animals and human tumor cells in culture. In clinical medicine, the reduced incidence of cancer among schizophrenic patients was attributed to neuroleptic medication. However, there has been little information on the effect of Se, carcinogen, and neuroleptic on the brain cells. This investigation was carried out on the brains of male Wistar rats treated with inorganic Se, 9,10-dimethyl-1,2-benzanthracene, and chlorpromazine. Chromatin was prepared and purified from isolated brain cell nuclei. Various protein species (histones and nonhistone proteins), RNA, and DNA were extracted by different extraction procedures. A higher relative content of nonhistone proteins was found in the group of animals treated with Se alone, carcinogen alone, and Se plus carcinogen administered simultaneously when compared with other experimental and control groups. The ratio of nonhistone proteins and histones of < 1.0 in the group of animals treated with neuroleptic + carcinogen or with neuroleptic indicates a lower content of nonhistone proteins when compared to histones. We obtained a more pronounced susceptibility to degradation by DNase I in the group of animals treated with neuroleptic + carcinogen or with neuroleptic compared to chromatin in the animals treated with carcinogen alone. We conclude that neuroleptic increases protein synthesis, as well as chromatin susceptibility to enzymatic degradation, thus achieving an opposite effect of carcinogen.