Inhibition of DNA and protein synthesis and cell division by photoactivated haematoporphyrin derivative in hamster ovary cells

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Abstract
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 [14C]-lysine incorporation were used to quantitate DNA and protein synthesis in surviving cells after exposure. Multiple experiments demonstrated 78% reduction in DNA synthesis during the first day after exposure to 20 micrograms ml-1 HpD plus 1140 Jm-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 approximately 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.