The development of anti-cancer drugs that are active in regions of low oxygen tension within solid tumours is an important goal for the chemotherapist. Equally as important is the utilization of appropriate model systems for their selection. This study describes morphological characteristics of multicellular spheroids derived from the human carcinoma cell line, DLD-1 and the evaluation of an investigational bioreductive alkylating agent (EO9) in monolayers, spheroids and xenografts. Histological examination of the cell line in vitro revealed typical features of glandular epithelium with microvilli on free surfaces and cell junction formation. Spheroids had acina formation, extensive necrosis and hypoxia at the time of treatment suggesting the spheroid model to be more representative of solid tumour geometry than more conventional in vitro test systems. EO9 is active against this cell line grown as a monolayer (IC50=0.76 mug ml-1) but is inactive against spheroids or established solid tumours in vivo. The suitability of this system for evaluating bioreductive drugs is discussed.

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