Dose-response relationships for photodynamic injury to murine skin.
Oedema and necrosis of murine tail skin have been measured after intravenous injection of haematoporphyrin derivative ("Photofrin", or PhI) followed 24 h later by graded exposures of the tail to full-spectrum visible light from a quartz-halogen lamp. End-points were degree of oedema and the proportion of mice in a dose-group that developed skin necrosis and tail atrophy. Oedema developed within 24 h of illumination and was a function of PhI dose and duration of light exposure. Onset of necrosis occurred after a minimum of 5 days and onset time was an inverse function of exposure time. Probit plots of proportion of necroses versus light exposure yielded values for ND50 (exposure corresponding to 50% incidence of necrosis) and l/slope. At the high but non-toxic dose of 2 mg PhI/mouse, ND50 was 18 min, l/slope 4 min, for pigmented BDF1 mice. Halving the PhI dose increased ND50 by a factor of 1.9. Albino BALB/c mice were markedly more sensitive to 2 mg PhI plus light than BDF1 mice: the ND50 was 7 min. Temporary occlusion of the blood supply to the tail (10 min before and during illumination) abrogated totally the oedematous and necrotic reactions to photodynamic therapy.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000209:etiology; D006414:Hematoporphyrin Photoradiation / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009336:Necrosis; D010778:Photochemotherapy / Q000009:adverse effects*; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D013997:Time Factors