PRECLINICAL IN-VITRO AND IN-VIVO ACTIVITY OF 5,6-DIMETHYLXANTHENONE-4-ACETIC ACID

5,6-Dimethylxanthenone-4-acetic acid (5,6-MeXAA) is a fused tricyclic analogue of flavone acetic acid (FAA) which was developed in an attemp t to improve on the activity of FAA. Previous studies have shown 5,6-M eXAA to be curative in 80% of mice bearing colon 38 tumours and 12 tim es more dose potent than FAA. This investigation has demonstrated that a murine colon tumour cell line (MAC15A) is approximately 60 times mo re sensitive to 5,6-MeXAA than to FAA, although these differences were not seen in three human cell lines tested. 5,6-MeXAA caused significa nt blood flow shutdown and haemorrhagic necrosis in subcutaneous MAC15 A tumours in syngeneic and nude hosts, but measurable changes in tumou r volume were seen only in syngeneic hosts. 5,6-MeXAA was inactive aga inst intraperitoneal MAC15A but produced significant anti-tumour effec ts against the same cell line inoculated via an intravenous route. FAA has been shown previously to be inactive in this model. Interestingly , the effects against lung colonies were not accompanied by obvious ne crotic changes, suggesting that they may be the result of increased di rect cytotoxicity rather than an indirect host mechanism. Further stud ies to investigate the effects against systemic tumour deposits are un der way.