Sper/NO-induced reversible proliferation inhibition and cycle arrests associated with a micronucleus induction in HSG...

Nitric oxide (NO) is an important messenger molecule with multiple biological activities. In the present study, sper/NO, a NO generator, showed a biphasic effect on the proliferation of human salivary gland neoplastic (HSG) cells. Sper/NO of less than 20 micro M stimulated cells to depart from the G2/M phase and so enhanced cell division and cell proliferation. But sper/NO at higher concentrations restrained cell proliferation and blocked cell-cycle progression. Cells were mainly arrested in the G2/M phase and S phase when they were treated with 100-200 and 300-500 micro M sper/NO, respectively. A special S-phase peak was detected in a histogram of the cell-phase distribution of sper/NO-treated HSG. When the concentration of sper/NO increased, the S-phase peak shifted from early the G2/M-phase to later the G1-S-phase boundary. Sper/NO-induced cell-cycle arrests were reversible when the cells were released from NO stress for 48h and hence cell proliferation was recovered. In addition, micronucleus, but no apoptosis, was produced in the sper/NO-treated cells, and its yield tended to a saturation value with increasing concentrations of sper/NO. The sper/NO-induced effects were effectively eliminated or reduced by treating cells with PTIO, a NO-specific scavenger, indicating that NO is the main source of these effects.