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

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.