THE UNPOLYMERIZED FORM OF TUBULIN IS THE TARGET FOR MICROTUBULE INHIBITION BY PHOTOACTIVATED TETRA(4-SULFONATOPHENYL) PORPHINE

Several porphyrins, including tetra(4-sulfonatophenyl)porphine, sensitize cells to photoinactivation. The treatment leads to an accumulation of cells in mitosis, directly or indirectly due to a perturbation of the mitotic spindle. The present work relates to the target for this mode of action. Cells incubated with tetra(4-sulfonatophenyl)porphine were exposed to light and the microtubules were quantified 30 min after light exposure. The amount of microtubules decreased with increasing fluences. The reduction in the amount of microtubules after light exposure was enhanced by prior treatment with nocodazole (1-mu-g/ml for 20 min) or low temperature (1-degrees-C for 60 min). When nocodazole was combined with the photochemical treatment the extent of the inhibition of microtubule formation was dose-dependent only for the lowest fluences applied. Additional light exposure did not further reduce the amount of microtubules 30 min after light exposure. The results presented indicate that the unpolymerized fraction of tubulin is the target for photochemical inhibition of microtubule formation.