Comparative skin phototoxicity in mice with two photosensitizing drugs: benzoporphyrin derivative monoacid ring A and porfimer sodium (Photofrin).
Benzoporphyrin derivative monoacid ring A (BPD-MA) and Photofrin (porfimer sodium) are photodynamic anticancer agents. The chemical structures of the two regioisomers of BPD-MA are 9-methyl trans-(+/-)-18-ethenyl-4,4 alpha-dihydro-3,4- bis(methoxycarbonyl)-4 alpha, 8,14,19-tetramethyl-4,4 alpha-dihydro-3,4- bis(methoxycarbonyl)-4 alpha, 8,14,19-tetramethyl-23H,25H-benzo(b)porphine- 9,13-dipropanoate and 13-methyl-trans-(+/-)-18-ethenyl-4,4 alpha-dihydro-3,4- bis(methoxycarbonyl)-4 alpha, 8,14,19-tetramethyl-23H,25H-benzo(b)porphine- 9,13-dipropanoate. Photofrin (a registered trademark of American Cyanamid Co.) is a polyporphrin oligomer containing ester and ether linkages. The ability of BPD-MA or Photofrin to cause skin phototoxicity was investigated in mice exposed to simulated sunlight (light) 3, 24, or 48 hr after receiving a single intravenous injection of vehicle or 2, 10, or 20 mg/kg of BPD-MA or Photofrin. The data were from two studies conducted using male and female CD1 mice (approximately 7 weeks old). The hair of the dorsal thoracic area was clipped 24 hr prior to exposure to light. Mice were exposed to light for 5 min. The clipped area of skin was the primary site for the evaluation of phototoxicity. Mice were observed for 2 weeks after treatment. There were no significant findings in controls or in mice given 2 mg/kg of BPD-MA. When mice were exposed to light 3 hr after dosing, both BPD-MA (10 or 20 mg/kg) and Photofrin (2, 10 or 20 mg/kg) caused phototoxicity. Death occurred in all mice given 20 mg/kg of BPD-MA or Photofrin, and in the majority of mice given 10 mg/kg of Photofrin.(ABSTRACT TRUNCATED AT 250 WORDS)
Wolford
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Medical Research Division, American Cyanamid Company, Pearl River, New York 10965.
Novicki
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Kelly
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D000818:Animals; D005260:Female; D017324:Hematoporphyrin Derivative / Q000633:toxicity*; D006414:Hematoporphyrin Photoradiation / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011166:Porphyrins / Q000633:toxicity*; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects; D012871:Skin Diseases / Q000139:chemically induced*; D013472:Sunlight
D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C504224:benzoporphyrin D; D017324:Hematoporphyrin Derivative