Sunlight has been implicated in the high incidence of
skin cancer found in patients receiving
6-mercaptopurine (PSH) in the form of its
pro-drug azathioprine. In this study we have used EPR spectroscopy in conjunction with the spin-trapping technique to determine whether PSH and its metabolic or photochemical oxidation products generate highly reactive
free radicals upon UV irradiation. When an aqueous anaerobic
solution (pH 5 or 9) of PSH (pKa = 7.7) and either
2-methyl-2-nitrosopropane (MNP) or
nitromethane (NM) were irradiated (lambda > 300 nm) with a Xe
arc lamp, the corresponding purine-6-thiyl (PS.) radical adduct and the reduced form of the spin trap (MNP/H. or CH3NO2.-) were observed. However, no radical adducts were detected when PSH and
5,5-dimethyl-1-pyrroline-N-oxide (DMPO) were irradiated (lambda = 320 nm) in
oxygen-free
buffer. These findings suggest that PSH does not photoionize but that instead MNP and NM are reduced by direct electron transfer from excited state PSH, 1.3(PSH)*. In aerobic
solution,
oxygen can act as an electron acceptor and the O2.- and PS. radicals are formed and trapped by DMPO.
6-Mercaptopurine did photoionize when irradiated with a
Nd:YAG laser at 355 nm as evidenced by the appearance of the DMPO/H.(eq- + H+) adduct, which decreased in intensity in the presence of N2O. 1.3(
6-Mercaptopurine)* oxidized ascorbate,
formate and
reduced glutathione to the corresponding ascorbyl, CO2.- or glutathiyl radicals. The photochemical behavior of
6-thioxanthine and
6-thiouric acid was similar to PSH. However, the excited states of these metabolic oxidation products exhibited stronger reducing properties than 1.3(PSH)*.(ABSTRACT TRUNCATED AT 250 WORDS)