Second Symposium Deemed a Success

Experiments were performed on cultured Chinese hamster ovary cells exposed to haematoporphyrin derivative (HpD) plus light, yielding survival rates of 40-100%. [3H]-thymidine, [3H]-tryptophan and ['4C]-lysine incorporation were used to quantitate DNA and protein synthesis in surviving cells after exposure. Multiple experiments demonstrated 78% reduction in DNA sysnthesis during the first day after exposure to 20pgml-1 HpD plus 1140Jm-2 light followed by progressive recovery to the normal rate after 4-6 days. Protein synthesis was somewhat less sensitive dropping by 54% initially and fully recovering by day 4. Although this cell line has a normal cycle time averaging 15 h, cell division was rarely observed among lone surviving cells until 72 h after exposure. No inhibition was observed in cells exposed to HpD in the dark. These results indicate that photoactivated HpD has a wide spectrum of reversible nuclear and cytoplasmic effects even at sublethal doses. This is consistent with the notion that clinical photodynamic therapy is not likely to result in chronic morbidity. The photosensitizing drug haematoporphyrin derivative (HpD) and light are demonstrating increasing promise in photodynamic therapy (PDT) for cancer (Dougherty, 1984). Unlike most other antineoplastic agents which act on intracellular metabolic and reproductive pathways taking time to kill target cells, photoactivated HpD can kill cells within minutes probably through production of singlet oxygen which lyses the cell membrane (Bellnier & Dougherty, 1982; Weishaupt et al., 1976). However, there is growing evidence that HpD plus light may have sublethal effects on other intracellular components in surviving cells. Haematoporphyrin (the less potent parent compound) and HpD plus light have been implicated in induction of sister chromatid exchange and chromosomal aberrations, but not in mutations (Gomer et al., 1983; Evensen & Moan, 1982; Moan et al., 1980). Cells experienced delay of progression through metaphase after treatment with HpD plus light (Christensen, 1981), division delay with depression of DNA synthesis (Moan et al., 1983), and variation in sensitivity through different phases of the cell cycle (Christensen et al., 1981). Photoactivated HpD has been shown to catalyse the breakdown of polynucleotides (Blazek, 1984). At the ultrastructural level it induces profound degenerative changes in mitochondria, ribosomes, endoplasmic reticulum and nuclear chromatin (Kato et al., 1984; Moan et al., 1982), and inhibits mitochondrial cytochrome c oxidase activity (Gibson & Hill, 1983). All effects were directly correlated with HpD dose and light exposure level. In the present work, the effect of sublethal doses of photoactivated HpD on …