PURPOSE: Irradiation of doxorubicin (DOX) dissolved in RPMI medium 1640 by long ultraviolet (UVA) light results in a rapid decline in the cytotoxic activity of the drug. The present study was designed to sort out which component(s) of this medium are associated with the UVA inactivation of DOX. METHODS: The effects of UVA irradiation of DOX in solutions of various compositions were evaluated by measuring the changes in the drug growth inhibitory activity in P388 cells and in the DOX absorbance spectrum. RESULTS: Riboflavin seemed to be the major photosensitizing component in the medium and the effect was enhanced by the presence of histidine, methionine, tryptophan and tyrosine but not by other amino acids. The changes in DOX resulting from UVA irradiation in the presence of riboflavin, were not blocked by 1,4-diazabicyclo [2.2.2]octane (5 mM), superoxide dismutase (300 units/ml), catalase (150 units/ml) or sodium benzoate (50 mM). The effects of UVA light on doxorubicin could be prevented by excess ascorbic acid. CONCLUSIONS: The effects of UVA on DOX are mediated by riboflavin. The photoexcited riboflavin apparently interacts directly with DOX rather than by first forming reactive oxygen species. The results suggest that the photoinactivation of DOX may involve an oxidation step. The mechanism by which certain amino acids facilitate the photoinactivation of DOX is not known. It is suggested that patient intake of riboflavin and exposure to the sun and fluorescent light could affect the outcome of anthracycline treatment.
PURPOSE: Irradiation of doxorubicin (DOX) dissolved in RPMI medium 1640 by long ultraviolet (UVA) light results in a rapid decline in the cytotoxic activity of the drug. The present study was designed to sort out which component(s) of this medium are associated with the UVA inactivation of DOX. METHODS: The effects of UVA irradiation of DOX in solutions of various compositions were evaluated by measuring the changes in the drug growth inhibitory activity in P388 cells and in the DOX absorbance spectrum. RESULTS:Riboflavin seemed to be the major photosensitizing component in the medium and the effect was enhanced by the presence of histidine, methionine, tryptophan and tyrosine but not by other amino acids. The changes in DOX resulting from UVA irradiation in the presence of riboflavin, were not blocked by 1,4-diazabicyclo [2.2.2]octane (5 mM), superoxide dismutase (300 units/ml), catalase (150 units/ml) or sodium benzoate (50 mM). The effects of UVA light on doxorubicin could be prevented by excess ascorbic acid. CONCLUSIONS: The effects of UVA on DOX are mediated by riboflavin. The photoexcited riboflavin apparently interacts directly with DOX rather than by first forming reactive oxygen species. The results suggest that the photoinactivation of DOX may involve an oxidation step. The mechanism by which certain amino acids facilitate the photoinactivation of DOX is not known. It is suggested that patient intake of riboflavin and exposure to the sun and fluorescent light could affect the outcome of anthracycline treatment.
Authors: Annette N Smith; Shawna Klahn; Brenda Phillips; Lisa Parshley; Peter Bennett; Andi Flory; Rosemary Calderon Journal: J Vet Intern Med Date: 2018-03-30 Impact factor: 3.333