silicon and Leukemia-L5178

A series of 12 organosilicon compounds representing potential intermediates in the synthesis and degradation of polydimethylsiloxanes were evaluated for genotoxic potential with a battery of in vitro assays. Microbial assays included the Ames bacterial reverse mutation in Salmonella, mitotic gene conversion in Saccharomyces cerevisiae D4 and DNA repair in E. Coli pol A +/-. These assays were conducted with and without a metabolic activation system containing Aroclor 1254-induced rat-liver homogenate. Forward gene mutation, sister-chromatid exchange, DNA alkaline elution and chromosome aberration potential were evaluated in mouse lymphoma L5178Y tissue culture cells. The tissue culture assays were performed with and without metabolic activation mixture utilizing uninduced mouse-liver S-9. The use of this enzyme preparation was felt to more closely mimic the actual in vivo situation and to be more compatible with mouse cells employed in the assay. No evidence of gene mutation was observed. However, six of the 12 compounds evaluated demonstrated potential in vitro clastogenic (chromosome damaging) activity.

Topics: Animals; Chromosome Aberrations; Dimethylpolysiloxanes; Escherichia coli; Leukemia L5178; Mice; Mutagenicity Tests; Mutagens; Saccharomyces; Salmonella; Silicon; Sister Chromatid Exchange; Tumor Cells, Cultured

Responses of the S/S variant of the L5178Y murine leukemic lymphoblast, the photoreceptor cell of the rabbit retina and the lenticular epithelium of the rabbit to heavy ions (20Ne, 28Si, 40Ar and 56Fe) are described and discussed primarily from the standpoint of the need for a comprehensive theory of cellular radiosensitivity from which a general theory of tissue radiosensitivity can be constructed. The radiation responses of the very radiosensitive, repair-deficient S/S variant during the G1- and early S phases of the cell cycle were found to be unlike those of normally radioresistant cells in culture: the relative biological effectiveness (RBE) did not increase with the linear energy transfer (LET infinity) of the incident radiation. Such behavior could be anticipated for a cell which is lacking the repair system that operates in other (normal) cells when they are exposed to ionizing radiations in the G1 phase of the cell cycle. The S/S variant does exhibit a peak of radioresistance to X-photons mid-G1 + 8 h into the cell cycle, however, and as the LET infinity was increased, the repair capacity responsible for that radioresistance was reduced progressively. Sensory cells (photoreceptors) in the retina of the New Zealand white (NZW) rabbit are very radioresistant to ionizing radiations, and several years elapsed after localized exposure (e.g., 5-10 Gy) to heavy ions (20Ne, 40Ar) before photoreceptor cells were lost from the retina. During the first few weeks after such irradiations, damage to DNA in the photoreceptor cells was repaired to a point where it could not be demonstrated by reorienting gradient sedimentation under alkaline conditions, a technique that can detect DNA damage produced by less than 0.1 Gy of X-photons. Restitution of DNA structure was not permanent, however, and months or years later, but before loss of photoreceptor cells from the retina could be detected, progressive deterioration of the DNA structure began. Age dependencies of late sequelae from densely ionizing radiations are matters of concern both for the therapeutic uses of radiation and the risk/benefit considerations of environmental exposure, especially in outer space. A pilot experiment with a single acute exposure to 20Ne ions has illustrated the need for careful examination of the role of animal age at the time of irradiation in subsequent tissue responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Argon; Cell Survival; Dose-Response Relationship, Radiation; Epithelium; Ions; Iron; Lens, Crystalline; Leukemia L5178; Mice; Neon; Photoreceptor Cells; Rabbits; Silicon