The eyes of a prospective cohort of 8,607 Chernobyl clean-up workers (liquidators) were assessed for cataract at 12 and 14 years after exposure. The prevalence of strictly age-related cataracts was low, as expected (only 3.9% had nuclear cataracts at either examination), since 90% of the cohort was younger than 55 years of age at first examination. However, posterior subcapsular or cortical cataracts characteristic of radiation exposure were present in 25% of the subjects. The data for Stage 1 cataracts, and specifically for posterior subcapsular cataracts, revealed a significant dose response. When various cataract end points were analyzed for dose thresholds, the confidence intervals all excluded values greater than 700 mGy. Linear-quadratic dose-response models yielded mostly linear associations, with weak evidence of upward curvature. The findings do not support the ICRP 60 risk guideline assumption of a 5-Gy threshold for "detectable opacities" from protracted exposures but rather point to a dose-effect threshold of under 1 Gy. Thus, given that cataract is the dose-limiting ocular pathology in current eye risk guidelines, revision of the allowable exposure of the human visual system to ionizing radiation should be considered.
The specific inhibitor of glutathione biosynthesis, L-buthionine sulfoximine (L-BSO), although relatively nontoxic in adult mice, induces severe glutathione depletion and age-specific pathological changes when repeatedly administered to male suckling mice. Dense cataracts developed when mice aged 9 to 12 days were given a series of injections of L-BSO, despite excellent survival and the absence of other significant long-term effects. By contrast, similar treatment of mice aged 14 to 17 days, although slightly less effective in reducing glutathione levels, resulted frequently in death, hind-leg paralysis, or impaired spermatogenesis, but did not produce cataracts. Administration of L-BSO to preweanling mice provides a novel model system for the induction of cataracts by depletion of lens glutathione and may enable the study of critical functions of glutathione in the lens and other growing tissues during early postnatal development.
Lens epithelial fragments (tags) recovered from individuals during routine cataract extraction have been assessed for cellular changes reflective of genotoxic damage. A high percentage of tags exhibited a population of micronucleated and polyploid cells. The presence and number of micronuclei (MN) in the epithelia of cataract patients appears to be independent of age and sex. However, a large number of MN in the epithelial cells of some individuals strongly suggests a history of compromised genomic integrity. While the study was not designed to define the role of DNA damage in the development of cataracts or to monitor human populations at risk of exposure to exogenous mutagens/cataractogens, the potential of the methodology to address each is demonstrated.
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