Carbon tetrachloride (CC1₄) was intraperitoneally injected into Balb/c mice 4 times at biweekly intervals, and the morphological changes of the liver and kidney were examined during 12 weeks after the last injection. The renal injuries progressed in spite of cessation of CC1₄ treatment; microcysts with tubular-cell degeneration were manifest on day 42 after the last injection of CC1₄. At the end of the experiment, however, interstitial fíbrosis with inflammatory cell infiltration was much more prominent. Glomerular changes with IgG deposits also developed following the tubulointerstitial changes. The CC1₄ treatment induced liver damage as well, but it promptly subsided without formation of cirrhosis. The CC1₄ nephrotoxicity was completely inhibited by whole body irradiation (200 rad) exposed at each injection of CC1₄. In contrast, the hepatic damage was not changed by irradiation. These results seem to indicate etiologic independence of renal and hepatic events induced by CC1₄ treatment. It is also suggested that chronic CC1₄ nephrotoxicity is mediated, at least in part, by radiosensitive responses of the mice themselves.

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Immunopathogenicity of trypsin-solubilized or non-solubilized renal tubular basement membrane (TBM) of the Lewis (LEW) rat was investigated. Autoimmune tubulointerstitial nephritis (TIN) was induced in BALB/c mice by immunization with trypsin-solubilized LEW rat TBM, while immunization with non-solubilized TBM did not produce the disease. Based on this preliminary experiment we studied the characterization of immunogenic and nephritogenic TBM antigen of the LEW rat. TIN was characterized by severe mononuclear cell infiltrates with multi-nucleated giant cells in the interstitium, tubular destruction and intensive IgG and C3 deposits along the TBM. Anti-TBM antisera and eluate from the nephritic mouse kidneys reacted with the TBM of normal LEW rat kidney by immunofluorescence. LEW rat TBM was also detected immunofluorescently by using antisera from BALB/c mice immunized with autologous trypsin-solubilized TBM. A competitive inhibition test revealed a higher titer of anti-TBM antibody in the eluate than in the adsorption-treated antisera per microgram IgG. Immunoblotting showed one reactive band with a molecular weight of 45,000 daltons, and the blotting patterns in tryptic TBM of the Brown Norway (BN) and LEW rats appeared similar. Amino acid analysis of nephritogenic LEW rat tryptic TBM showed that it contained no hydroxyproline and hydroxylysine, suggesting that this TBM preparation was not collagenous. These findings suggest that tryptic digestion contributes to the release of nephritogenic antigen from the LEW rat TBM and that this antigen system might participate in the immune system involved in the anti-TBM associated TIN that is well known to be induced by non-digested TBM of TBM antigen positive animals.

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