Genetic toxicology of the photosensitization of Chinese hamster cells by phthalocyanines.

Abstract

Chloroaluminum phthalocyanine (CAPC) was recently shown to photosensitize cell killing in culture and tumor destruction in vivo. Because this compound is potentially useful in the photodynamic therapy of cancer, its properties as a genotoxic agent were evaluated. Applying the technique of alkaline elution to study DNA integrity, it was found that CAPC could produce single‐strand breaks in the DNA of Chinese hamster cells after exposure to white fluorescent light. At equicytotoxic doses, the number of DNA strand breaks produced by CAPC photosensitization was about three times lower than that induced by X‐irradiation. During incubation in growth medium after exposure to CAPC‐plus‐fluorescent light, cells rejoined DNA strand breaks at a rate similar to that observed after X‐irradiation. Resistance to 6‐thioguanine (6‐TG') or to ouabain (OUA') were used as end points of mutagenic potential. Following a treatment that caused ‐90% cell killing, there was a slight mutagenic effect, i.e. the frequencies were increased by ‐40% above the background or spontaneous mutations. However, this enhancement was not statistically significant. Taken together, the foregoing, plus an earlier observation that there is no variation in the sensitivity of cells to CAPC + light through the cell cycle, lead to the inferences that DNA damage does not play a major role in cell killing and that the mutagenic potential of this treatment is small.