This study was designed to investigate the hypothesis that the inhibition of
ferrochelatase will cause in situ build up of high concentrations of
protoporphyrin-IX which may act as a putative agent for photodestruction of
cancer cells. The parenteral administration of
lead acetate, a known inhibitor of
ferrochelatase, to mice bearing cutaneous
tumors (
papillomas and
carcinomas) caused a six-fold enhancement in the concentration of
protoporphyrin-IX in
tumors within a period of one month. Forty-eight hours after the second injection of lead, mice were exposed to visible light, at a light dose of about nine kilo lux for a period of one hour (in four sittings of fifteen minutes each keeping a gap of ten minutes between two exposures). A significant reduction in
tumor size was observed starting as early as day one following the treatment. Continuous treatment for six consecutive days resulted in almost complete ablation of the
tumor mass in most of the animals. Complete regression of the
tumors was observed at two to three days following the first exposure. Our observations on in situ accumulation of
protoporphyrin-IX by
heme-biosynthesis inhibition represent a novel method for
photodynamic therapy of
cancer cells. It is important to emphasize that lead is a fairly toxic agent and developing a non-toxic agent is one of our future goals.