The effectiveness of short-term versus long-term exposures to Photofrin II in killing light-activated tumor cells.

Asynchronous populations of mouse EMT-6 tumor cells were exposed to various doses of 630-nm light in slowly stirred aerobic suspensions after both short-term and long-term exposures to Photofrin II. All survival curves are characterized by a "threshold" light dose below which no cell inactivation occurs followed by a steep light-dose response. Both the shoulder widths and the inactivation curve slopes are functions of Photofrin II concentration. After high doses of light where survival levels are 0.003 and lower, "resistant tails" are observed on some survival curves. Light doses required to inactivate 50% of tumor cell populations were obtained from whole survival curves and their reciprocals ( $1/D_{50\%\ \text{survival}}$ ) used as inactivation "rates." The amount of Photofrin II within cells was measured by a fluorescence assay. Per unit of fluorescence, this photosensitizer is at least 10 times more effective after long-term than after short-term exposures. After long-term exposure...