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  • Title: In vitro activity of the benzotriazine dioxide SR 4233 against human tumour colony-forming units.
    Author: Hanauske AR, Ross M, Degen D, Hilsenbeck SG, Von Hoff DD.
    Journal: Eur J Cancer; 1993; 29A(3):423-5. PubMed ID: 8398345.
    Abstract:
    SR 4233 (3-amino-1,2,4-benzotriazine 1,4-dioxide) is a novel bioreductive agent selectively toxic to hypoxic cells. It is active as a radiation sensitiser in vitro. Using a human tumour cloning system we have studied the effects of SR 4233 against freshly explanted human tumour specimens under hypoxic and non-hypoxic culture conditions. For hypoxic conditions, final concentrations of SR 4233 of 10.0-500 mumol/l were used in short-term (1 h) exposure experiments. Final concentrations in non-hypoxic experiments ranged from 10 to 1350 mumol/l. 25 tumour specimens were tested under each culture condition. Of those, 14 (56%) were evaluable. The most common tumour types recruited included ovarian, non-small cell lung, and breast cancer. A moderate concentration-dependent increase in the frequency of inhibited tumour specimens under non-hypoxic conditions was observed with zero out of 10 sensitive specimens at 10 mumol/l as compared with five out of 14 (36%) sensitive specimens at 500 mumol/l (P < 0.02). However, when hypoxic conditions were used SR 4233 had a profound antitumour activity, (two out of 14 specimens sensitive at 10 mumol/l compared with 10 out of 10 specimens sensitive at 500 mumol/l, P < 0.00005). We conclude that SR 4233 is active against tumour colony-forming units in vitro and that its antitumour activity is greatly increased against hypoxic tumour cells.
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