Induction of antinuclear antibodies by ultraviolet irradiation.

Ultraviolet (UV) irradiation or exposure to sunlight are well known but poorly understood predisposing factors of systemic lupus erythematosus (SLE) (Dubois, 1966; Freeman, Knox, and Owens, 1969). It appears from the published literature, that little attention has been paid to what actually occurs when apparently healthy individuals are exposed to UV irradiation. On a molecular level, UV irradiation of DNA is known to cause, among other things, dimerization of adjacent thymine groups in the DNA molecule (Setlow, 1968). Micro-organisms and also some species of higher animals possess enzymatic mechanisms which protect them against the influence of UV light (Setlow, 1968; Freeman, Troll, and Knox, 1968; Cleaver and Painter, 1968; Cook and Regan, 1969). One of these mechanisms is dependent on energy offered by light of longer wave-length than that of the damaging radiation. This process, which is called photoreactivation, splits the thymine dimers, thus restoring the original structure of the DNA molecule (Setlow, 1968). Another consequence of UV irradiation of DNA is that the DNA molecule, which is normally a very weak antigen, becomes a strong one. After the injection of UV-irradiated DNA (UV-DNA) into rabbits, antibodies with high titres against UV-DNA are found (Levine, Seaman, Hammerschlag, and van Vunakis, 1966). We found that after prolonged immunization the sera of 6 rabbits cross-reacted with normal nonirradiated DNA, in low titres. When determined with a complement-fixation technique, the anti-UV-DNA titres varied between 1/512 and 1/1024 and the anti-DNA titres between 1/16 and 1/64. This strong antigenic ability of UV-DNA led us to investigate the effects of UV irradiation on mice. Since ther are indications that a photoreactivation-like process might exist in mice (Freeman and others, 1968), a model was chosen in which a possible influence of daylight could be observed. Material and methods