Phototoxicity of brain tissue in hematoporphyrin derivative treated mice

Photoradiation therapy conditions which have been used to treat subcutaneous and breast tumors are lethal when applied to the head of mice. Treatment of control mice with laser light at 631 nm over an energy density range of 0-90j/cm2 had no measurable effect but mice photosensitized with 5 mg HPD/kg 72 hrs prior to laser treatment showed a threshold for brain damage at 56j/cm2, above which the mice developed cerebral edema and died. Laser treatment caused the same rate and magnitude of temperature rise in both control and HPD-photosensitized mice. Moreover, studies using mice whose brain temperature was kept below 37 degrees C during laser treatment showed a greater phototoxicity than mice without temperature regulation. Therefore, temperature rise in cerebral tissue was not associated with phototoxicity in the brain. In contrast the oxygen consumption rate in a brain cell suspension from an HPD-treated mouse was only 54% of that from a control mouse following treatment with laser light. This observation, when taken with supporting data from other investigations, suggests that one mechanism for the phototoxic response in brain tissue is oxygen deprivation resulting from mitochondrial damage.