CONTROL OF HEXOSE TRANSPORT IN CULTURED RETINOBLASTOMA

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The lens protein "crystalline" can be subject to various types of disorders. It is known that juvenile diabetes mellitus or various types of galactosemia bring about cataracts. The basis for these cataracts has often been ascribed to an entrapment of glucose or galactose by transport into the lens and subsequent enzymatic reduction into the corresponding polyols by the huge excess of sugar reductases. This state of affairs creates osmotic imbalance, due to the fact that the accumulating polyols seem not to have a facilitated efflux but have to diffuse out passively. The ensuing hyperosmosis would eventually draw water into the finely ordered crystalline of the lens and thus create a lens cataract. This seems to be the main factor in juvenile cataracts. What type of hexose transport system drives glucose or galactose into the lens and how is it regulated if at all? Hexose transport systems in fibroblast or myoblast cultures which can be downregulated by glucose are commonly observed. We shall call this down- regulation the transport "CURB". We have studied the transport curb in various lines of hamster lung fibroblast cultures. We obtained a particularly clear insight by using a mutant, the PGI mutant, because it lacks phospho-gluco-isomerase. This means that glucose-6-P cannot be converted to fructose-6-P a conversion which critical for the generation of aerobic energy metabolism which is essential for the transport curb. The PGI mutant shows a strong curb only with glucose, but not with mannose, glucosamine nor fructose. Surprisingly enough, the all- cis aldohexose, D-allose, turned out to be the most effective transport "curber"; D-altrose was inactive. Further progress depends on the availability of radiolabelled D-allose. Our finding that tunicamycin (TN) further intensifies the glucose or allose- induced curb (85% loss of transport capacity vs. fructose medium) is noteworthy so much the more since a switch from allose to fructose restores half the transport capacity within 6 hrs regardless of the presence or absence of TN. It would be of great interest to compare the hexose tansport systems of the lens with that of retina preps or cultures from retinablastoma, in regard to the mediated glucose-TN curb. A few hrs. preincubation followed by the usual transport test will be tried.