Effect of adroxazine, a heterocyclic compound of the adrenals, on the rate of replication of lymphoblastoid cells

Abstract

It has been found that the addition of 10−2–10−8 μL/mL of adroxazine, a heterocyclic compound of the adrenals, to the tissue culture medium increases the rate at which three strains of lymphoblastoid cells replicate. For example, the addition of 10−5 μg/mL of adroxazine to cultured L5178Y cells decreases their doubling time from approximately 11 to 8 h and addition of 10−3 μg/mL of adroxazine to the tissue culture medium of Huly-16 or Huly-29 cells decreases their doubling time from approximately 43 to 34 and 36 h, respectively. Other concentrations of adroxazine, from 10−2 to 10−8 μg/mL, cause a less but measurable decrease in doubling time. The effect of adroxazine on the rate of incorporation of [3H]thymidine into acid-precipitable material by lymphoblastoid cells was found to parallel the effect of adroxazine on doubling time. The effect of adroxazine on the length of DNA synthesis and mitosis was calculated from the percent of cells that are labeled with [3H]thymidine during a 20-min interval and the percent of cells in mitosis, respectively. Results showed that adroxazine does not decrease the length of DNA synthesis or mitosis, but markedly decreases the sum of pre- and post-mitotic resting times [Formula: see text]. Addition of 10−3 μg/mL of adroxazine to the medium decreases the resting times of Huly-16 cells from approximately 20 to 10 h and Huly-29 cells from approximately 12 to 5 h. Addition of 10−5 μg/mL of adroxazine to the medium decreases the resting time of L5178Y cells from 3.3 to 0.1 h. The effect of adroxazine on [Formula: see text] and [Formula: see text] was calculated by using the fraction of labeled cells in mitosis method. It was found that adroxazine markedly decreases the mean duration of both [Formula: see text] and [Formula: see text].