Involvement of reversible binding to α2u-globulin in 1,4-dichlorobenzene-induced nephrotoxicity

摘要: Abstract Similarly to unleaded gasoline, 1,4-dichlorobenzene (1,4-DCB) administered for 2 years caused a dose-related increase in the incidence of renal tumors male but not female rats or either sex mice. Unleaded gasoline and 2,2,4-trimethylpentane (TMP), component increased protein droplet formation cell proliferation rat kidneys. These droplets contained, α 2u -globulin, rat-specific low-molecular-weight 2,4,4-trimethyl-2-pentanol, metabolite TMP that was reversibly bound this protein. Studies were undertaken determine if 1,4-DCB produced similar effects; 1,2-DCB used comparison since it did produce carcinogenesis rats. Gel filtration chromatography 116,000 g supernatant prepared from kidneys 1,4-[ 14 C]DCB-treated showed radiolabel coeluted with -globulin as one sharp peak opposed multipeak pattern observed 1,2-[ C]DCB; maximal quantity twice 1,2-DCB. Equilibrium dialysis kidney cytosol presence absence sodium dodecyl sulfate demonstrated -globulin; amount almost much also shown be covalently liver plasma high-molecular-weight proteins. and, minor extent, 2,5-dichlorophenol, major 1,4-DCB, 1,4-DCB-treated kidneys, whereas equimolar doses no effect sex. Renal proliferation, measured by [ 3 H]thymidine incorporation into DNA, after treatment. Nephrotoxicity biochemical alterations induced resemble those suggest mechanism is involved induction nephropathy