Deoxyspergualin, a potent antitumor agent: further studies on the cytobiological mode of action.

Under otherwise identical conditions, deoxyspergualin preferentially inhibits the growth of the T-cell leukemia line L5178y; an effective dose for a 50% inhibition (ED50) of 0.0007 microM was determined. A much weaker cytostatic activity was found for murine lymphocytes (ED50: approximately 25 microM) and for CV-1 monkey kidney cells (ED50: 16.3 microM). Deoxyspergualin causes biphasic and differential effects on DNA metabolism of murine T and B lymphocytes. At lower concentrations (0.3 approximately 5 microM) the [3H]TdR incorporation into nonactivated or lipopolysaccharide-activated lymphocytes is significantly stimulated by the compounds; this effect was not observed with lymphocyte cultures stimulated with concanavalin A. This change of TdR incorporation rates was found to parallel with the variations of DNA polymerase alpha activity. Deoxyspergualin causes an additive effect together with bleomycin and a significant synergistic cytostatic effect in combination with avarol and avarone. Moreover, it is reported that deoxyspergualin causes neither a selective inhibitory effect on DNA-, RNA- or protein synthesis nor an alteration of the intracellular distribution pattern of the Ro and La antigens. However, detailed enzymic studies revealed that deoxyspergualin reduces DNA polymerase alpha but not beta activity in lymphocytes at the ED50 concentration of this compound. These results support previous documentations that deoxyspergualin is of potential clinical usefulness (a) in treatment of certain tumors and (b) in organ transplantation.