Growth stimulation by misonidazole of lung carcinoma cells maintained in continuous organotypic and monolayer cultures.

Inasmuch as misonidazole is a drug used in clinical trials for sensitizing radioresistant hypoxic cells in solid tumors, it seemed of interest to study its effects in human tumor cells maintained in tridimensional organotypic cultures. This type of culture involves: spatial organisation of the cells with fairly undisturbed differentiation patterns, minimal traumatizing culture conditions, and offers the possibility to follow post-treatment growth patterns over several months without disturbing the cultures. Misonidazole exhibited a radiosensitizing effect on irradiated nodules derived from a lung adenocarcinoma, and on cells of this tumor growing in monolayers. However, after a 4 hour contact with misonidazole at concentrations corresponding to the range of those found in the serum of treated patients, a significant stimulation of nodule growth was repeatedly observed, together with a strong increase in the frequency of sister chromatid exchanges. Similarly, after treatment of the same tumor cells in confluent monolayers, their colony forming ability was increased. These observations may account for some of the non- convincing therapeutic results obtained in clinical trials.