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Previous studies have shown that human IgG1 contains a ‘reactive’ disulfide bridge (SS*), detectable by a 24-hour disulfide exchange reaction, and that the serum level of this IgG subclass is selectively diminished in patients with various malignant diseases. Here we present evidence that in rats IgG2b is the only subclass that carries one SS* per molecule. Furthermore, it is shown that rats inoculated with experimental tumor lines, i.e., the Yoshida hepatoma ascites tumor and the Walker 256 carcinosarcoma growing in ascites or as solid tumor, exhibit significantly decreased SS* per mole IgG which corresponds to a selective diminution of IgG2b. Although at later stages there is a quantitative correlation with the tumor burden, with the Walker tumor this effect becomes significant as early as 24 h after inoculation, i.e., well before exponential tumor growth and an absolute reduction of total IgG. Control animals injected intraperitoneally with either viable spleen cells or irradiated Walker 256 cells did not show comparable alterations in their IgG subclass profile. Thus, the selective defect of IgG2b requires the presence of viable and proliferating tumor cells. Possible mechanism(s) of tumor-associated shifts in IgG subclasses are discussed.

The purpose of this study was to determine firstly whether the isolated enzyme DNA polymerase alpha, which functions within the DNA replicase system, exhibits different sensitivity against the thiol-blocking agent 4-hydroxy-nonenal (HNE) when adult rat liver and the rapidly dividing Yoshida ascites hepatoma were used as enzyme sources and, secondly, whether the reaction catalysed by DNA polymerase is the most sensitive step of the DNA replicase system of native cells. DNA polymerase alpha as well as the non-replicative DNA polymerase beta, isolated from both sources, were remarkably similar with regard to their sensitivity against HNE, as indicated by the incorporation of radioactive label from [3H]deoxy-thymidine-triphosphate into DNA. The transport of [14C]thymidine through the plasma membrane and the incorporation of this precursor into DNA were studied with neonatal hepatocytes and with hepatoma cells. The incorporation of thymidine was inhibited at lower concentrations of HNE in both cell lines than the transport process and the reaction catalysed by DNA polymerase alpha. It was concluded that in the DNA replicase system of native liver and hepatoma cells another process different from the reaction catalysed by DNA polymerase alpha is more sensitive to HNE.

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