The ERRL of Columbia University is a facility uniquely equipped and staffed to realize its long term commitment to: 1) Assess the cataractogenic risk to the lens from exposure to ionizing radiation. 2) Elucidate the mechanism by which radiation produces cataracts. 3) Exploit the similarity between experimental radiation cataracts and some types of human cataracts to gain insight into the nature of the cortical opacification in general. In adhering to that committment the proposed studies will involve a greater emphasis on lens damage from 450 MeV/amu iron (56Fe) ions. Inasmuch as 250 kVp X-rays will serve as the reference radiation throughout the studies the investigations will compliment previous inquiries into X-ray cataractogenesis. Following irradiation, rats will be followed for their lifespans using the Zeiss Scheimpflug Slit-lamp Imaging System. This will provide, for the first time, an ojbective, permanent and fully quantifiable record of radiation cataract development and thereby will reduce the ambiguity in the analysis of cataract data generated during this longitudinal study. The investigation will concentrate on the extent and mechanism of the enhancement of cataractogenic potential observed when doses of heavy particles are administered in fractions. The exacerbation of the cataractogenic effect is important, not only from the standpoint of safety, but also because it offers a means to address some fundamental aspects of the response of normal tissues to radiation. We plan to expand our investigations on the cellular basis of radiation cataract development and will concentrate on the target population, the lens epithelium. A number of parameters known to be affected by ionizing radiation will be fully assesssed using automated scanning photometry as a function of the dose, time post-irradiation and nature of the radiation. The determinations will include effects of the radiation on the cell cycle, DNA content, cell killing and mutagenesis. These data are critical to an understanding of the mechanism of radiation action on the lens in particular and normal tissue in general. The findings from the proposed studies will contribute greatly to our understanding of cortical cataractogenesiss of varying etiologies, including age, and will directly impact the assessement of radiation risk from radiation therapy, occupational exposure and in the space program.
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