A novel organoselenium compound,WB（1,2-[bis（1,2-benzisoselenazolone-3（2H）-ketone）]pentane） has indicated anti-tumor activity.Its pharmacokinetic data has never been determined.By using the H22 tumor bearing mouse model,the tissue distribution of WB after single and four consecutive doses（both were 120 mg/kg/d） was explored.The selenium content of the tissues was used as an indicator of WB absorption,distribution and metabolism.The selenium in the heart,liver, spleen,kidneys,lungs,stomach,pancreas,brain,colon,intestine,testes,plasma,and tumor were determined by generation atomic fluorescence spectrometry（AFS）.With single or multiple oral administration of WB,the selenium content significantly increased in the liver,stomach,colon,and intestine.The selenium content in the spleen,lungs,pancreas,testes,plasma and tumor also increased compared with the controls;but no significant changes were found in the brain and kidney.WB and its metabolites distributed predominantly in the colon,liver,stomach and intestine,which resulted in a significant increase in the selenium content in both groups.There was no observed significant accumulation of WB in the vital organs.
As a synthesized antineoplastic organoselenium compound, ethaselen is known to induce apoptosis in tumor cells via dose-dependent thioredoxin reductase （TrxR） inhibition. Thioredoxin, the multifunctional biological substrate of TrxR, is then left in the oxidized state, which subsequently leads to intracellular accumulation of reactive oxygen species （ROS）, cell cycle arrest and/or apoptosis. However, the low dose effect of ethaselen remains largely unknown. Several subclones have been derived from HepG2 cells by using single cell or colony isolation. The low dose of ethaselen was defined as the drug concentration of retaining 〉90% HepG2 cells alive. The HepG2 cells were used as reference of its subclones （SM01, SM02 and SM03）, and the cell cycle transition, intracellular proteins change, colony formation and sphere growth were assayed in treatment of low dose ethaselen. HepG2 and its subclones differently responded to lethal dose of cisplatin or 5-fluorouracil. Low dose of ethaselen （1 μm） modulated the cell cycle transition at 12 h of treatment, but ceils were partially recovered at 24 h of treatment though some proteins were still affected. Low dose of ethaselen did not inhibit the small colony （diameter 〉 100 μm） formation and sphere growth of HepG2 and SM01. However, low dose of ethaselen could specifically inhibit the survival, large colony （diameter 〉500 μm） formation and sphere growth of SM03, although SM03 could be rapidly recovered from ethaselen-induced cell cycle check. HepG2 and its subclone cells could survive but respond differently to treatment of low dose ethaselen （1 μM）. Low dose of ethaselen could significantly inhibit a HepG2 subclone （SM03） in cell survival and colony growth.
