The effect of caffeine on alkylation-induced cell death, mutations and chromosomal aberrations in Chinese hamster cells : Roberts, J. J., Chester Beatty Research Institute, Institute of Cancer Research, Pollards Wood Research Station, Chalfont St. Giles, Buckinghamshire (Great Britain)

Abstract

Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases in humans characterized by the loss of photoreceptor cells leading to reduction of the peripheral visual field (known as tunnel vision) and eventually to blindness. N-Methyl-N-nitrosourea (MNU) is an alkylating agent that exhibits its toxicity by transferring its methyl group to nucleobases in nucleic acids. A single systemic administration of MNU causes retinal degeneration in various animal species. The retinal degeneration is highly reproducible, and the photoreceptor cell loss occurs within a week when a suitable dose of MNU is administered. Photoreceptor cell loss occurs via apoptosis, which resembles human RP. Decreased levels of basal autophagy concomitantly occur during the course of apoptosis progression. The time-course progression of the disease, the molecular mechanisms of the disease, and the therapeutic trials against MNU-induced photoreceptor cell apoptosis are described.