Suppression of the modulatory effects of the antileukemic and anti-human immunodeficiency virus compound avarol on gene expression by tryptophan.

The amino acid L-tryptophan is known to be a modulator of many processes of cell metabolism. In this contribution we show that i.- tryptophan interferes with some biological effects of the antileukemic and anti-human immunodeficiencyvirus agent avarol, possibly by differ ent mechanisms. Avarol has been shown to be able to modulate posttran- scriptional events of mRNA synthesis, resulting in an increase of the base-sequence complexities of the nonabundant and rare mRNA classes. Here it is demonstrated that this change in mRNA abundancy distribution is accompanied by an increase in the level of some specific, low abundant mRNAs (ras and c-myc). Addition of L-tryptophan was found to abolish avarol-caused gene relaxation in 1,1210mouse leukemia cells. In addition, L-tryptophan suppressed the induction of -y-interferonmRNA production in human peripheral blood lymphocytes. At the level of DNA, L-trypto phan inhibited the production of strand breaks by cytotoxic avarol concentrations in Friend erythroleukemia cells in vitro. Moreover, it competed with avarol for binding to the nuclear envelope binding site; this effect was not shown by other amino acids.