Novel anti-carcinogenic activity of an organosulfide from garlic: inhibition of H-RAS oncogene transformed tumor growth in vivo by diallyl disulfide is associated with inhibition of p21H-ras processing.

In this study, we report a novel anticarcinogenic activity of an organosulfur compound from garlic, diallyl disulfide (DADS). DADS treatment significantly inhibited the growth of H-ras oncogene transformed tumors in nude mice. As compared to controls, the appearance of tumors was also delayed markedly by oral administration of DADS. The inhibition of tumor growth by DADS treatment correlated with the inhibition of p21H-ras membrane association in the tumor tissue. The levels of membrane associated p21H-ras were markedly lower in the tumor tissues of DADS treated mice as compared to controls. An opposite trend, however, was evident for cytosolic p21H-ras. Furthermore, DADS treatment resulted in a significant inhibition of hepatic as well as tumoral 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. These results indicate that DADS suppresses the growth of H-ras oncogene transformed tumors in nude mice by inhibiting the membrane association of tumoral p21H-ras.

Sub-threshold near-UV radiation effects on aphakic guinea pig retinas.

Monocularly aphakic guinea pigs (Cavia porcellis), prepared by removing the lens by phacoemulsification, were maintained under near-UV lighting conditions for several months. Exposure to near-UV energy was at much lower irradiance levels than that of sunlight, and was at lower than the threshold level for near-UV damage to the aphakic monkey retina as reported by Ham, et al (1). In some aphakic eyes, regenerated lens-like structures formed which scattered light appreciably. After increasing light exposure periods, the eyes of control and irradiated animals were studied histologically. Other animals were periodically examined by electroretinographic (ERG) techniques. While there was no observable histopathological damage, aphakic-UV irradiated eyes with little or no lens regrowth exhibited depressed b-waves, late time constants and altered wave forms when compared with control eyes. The results demonstrate that ambient near-UV light exposure can adversely influence retinal electrical activity in aphakic eyes at irradiance levels below threshold for morphological damage. The protective function of the lens is also supported by these findings.

Lack of photosensitization of ocular tissues by allopurinol.

Based on careful double-blind studies using albino mouse ocular tissues, we conclude that allopurinol does not act as a photosensitizer for ocular tissue damage in mice relative to exposure to environmental near ultraviolet (UV) light. Damage to lens epithelial cells and retinal photoreceptors was equivalent in UV light-exposed mice that were either fed or not fed a dose of allopurinol equivalent to that used by humans in the treatment of gout. There was also no direct in vitro photosensitizing interaction between allopurinol and protein or nucleic acids. We conclude that patients in whom cataracts developed after using allopurinol and exposure to high irradiances of near UV light were most likely affected by the UV light itself.