The effect of
chlorozotocin [(CZT) CAS: 54749-90-5; 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-gluco-pyranose] was studied on a series of tumor cells, cultured or extracted fresh primary or transplanted
tumors, by means of clonogenic assay. The ability of most rat
rhabdomyosarcoma cells to form colonies in soft
agar was enhanced when exposed to the water-soluble nitrosourea
chloride CZT. The
tumor cells tested were derived from a) several primary
tumors induced in WAG rats by colloidal
nickel, then cultured and exposed to CZT early during in vitro passage; b) the 9-4
tumor, also Ni-induced but maintained in long-term culture; and c) the Ni-induced 9-4/0
tumor, maintained by
transplantation in syngeneic rats. No inhibition of colony formation was observed in any of the cell lines even at high concentrations of CZT.
Adriamycin, chosen as a control treatment, strongly inhibited the cloning efficiency (CE) of the
tumor cells. In vivo, the weekly injection of 10 mg CZT/kg
body weight into syngeneic rats bearing transplanted
tumors led to an enhancement of lung
metastasis formation. The CZT enhancement of CE of
tumor cells and its relationship to increased in vivo
tumor metastasis is discussed.