Survival and cycle-progression delay of cultured human lymphoma cells treated with 1-propanol, 3,3'-iminodi-, dimethanesulfonate (ester), hydrochloride (Yoshi 864).
Asynchronous human lymphoma cells treated for 1 hour with increasing concentrations of 1-propanol, 3,3'-iminodi-, dimethanesulfonate (ester), hydrochloride (Yoshi 864) revealed a shouldered survival curve typical of the effects of alkylating agents and of ionizing radiation on this cell line. Yoshi 864 was unstable under the conditions of treatment, its killing effect being reduced by 50% after only 4 hours. Synchronized cells showed stage-dependent sensitivity: early-S, late-G2, and late-G1 phases were the most sensitive while mid- and late-S and early-G2 phases were relatively insensitive. Yoshi 864 induced a concentration- and incubation time-dependent delay in the transit of asynchronous cells through G2 phase, with maximum accumulation values obtained after 12 hours of incubation with 100 mug/ml. This effect was largely reversible and no further kinetic changes were noted in the progeny of treated cells. Incubation of synchronized cells for 1 hour with 100 mug/ml demonstrated a block in G2, the manifestation of which during the lifespan of the treated cell or in its immediate progeny was cell-cycle dependent. Thus, cells treated in G1, early-, and mid-S phases showed a delay in the subsequent G2 phase while cells treated in late S and in G2 manifested this effect in the G2 phase of the immediate progeny. There was no correlation between this blocking effect in G2 with cell survival assessed by colony formation. Yoshi 864, although a rather inefficient killing drug, may represent a useful chemical synchronizing agent.
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008223:Lymphoma / Q000378:metabolism*; D008698:Mesylates / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology
D008698:Mesylates; D011437:Propylamines; C001441:improsan