Vitamin B6 phototoxicity induced by UVA radiation.
We have previously reported that pyridoxine shows UVA-induced cytotoxicity. Four other vitamin B6 compounds (pyridoxal, pyridoxamine, pyridoxal phosphate, and pyridoxamine phosphate) are metabolically more important in vivo than pyridoxine. These compounds were examined for UVA phototoxicity to cultured human fibroblasts. The cytotoxicity was measured by post-UVA irradiation colony-forming ability. All the B6 compounds except pyridoxal phosphate showed cytotoxicity. Pyridoxamine phosphate, which is the most important form of vitamin B6 in vivo, had the strongest cytotoxic effect. To examine the involvement of reactive oxygen species in the phototoxicity, we performed an electron spin resonance study using the spin trapping agent, 5,5-dimethyl-1-pyrroline N-oxide, and diethylenetriaminepentaacetic acid. We failed to detect radicals derived from vitamin B6. The cytotoxic effect remained in UVA-irradiated solutions for at least 30 min after the end of UVA irradiation. Hydrogen peroxide was produced in the solution, but the amount was not enough to cause cytotoxicity. In addition, the cells from xeroderma pigmentosum patients who belong to group A or C showed survival curves similar to those of normal fibroblasts. This suggests that cyclobutane pyrimidine dimers or 6-4 photoproducts of DNA were not involved in this damage. These findings suggest that UVA-induced vitamin B6 cytotoxicity is caused by toxic photoproducts resulting from irradiated vitamin B6.
Maeda
T
T
Department of Laboratory Medicine and Pathology, Faculty of Medicine, University of Alberta, Edmonton, Canada. tmaeda@ualberta.ca
Taguchi
H
H
Minami
H
H
Sato
K
K
Shiga
T
T
Kosaka
H
H
Yoshikawa
K
K
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D004578:Electron Spin Resonance Spectroscopy; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D011730:Pyridoxal / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D011733:Pyridoxamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011736:Pyridoxine / Q000494:pharmacology*; D014466:Ultraviolet Rays
D011730:Pyridoxal; D011732:Pyridoxal Phosphate; D011733:Pyridoxamine; D011736:Pyridoxine; C010627:pyridoxamine phosphate; C024593:pyridoxine 5-phosphate