ACTIVITY OF SYNGENEIC COMPLEMENT FOR REVEALING ANTIBODY-INDUCED CYTOTOXICITY AGAINST A RAT HEPATOMA

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Abstract

Summary

The cytotoxicity of tumour-bearer serum against a transplanted aminoazodye-induced rat hepatoma was revealed using normal rat serum as the source of complement as assessed using a short-term 51Cr release test. The tumour-bearing rat was not deficient in a functional complement system and direct cytolysis against hepatoma cells was demonstrated following admixture of tumour cells and serum with no additional complement. No tumour growth was observed in animals receiving subcutaneous transfer of cells treated with tumour-bearer serum, although when heat-inactivated (56 C for 60 min) or normal sera were used, there was no modification of tumour development.

The present findings indicate that the tumour-bearing animal contains both antibodies and complement sufficient for tumour lysis, although the full contribution of serum-mediated cytotoxicity in imposing immunological constraints upon tumour growth remains to be elucidated.

Complement-dependent antibody-induced cytotoxicity against a variety of chemical- and virus-induced neoplasms has been reported using isotopic and nonisotopic techniques to assess cell survival (1–12). In each of these studies, heterosera (usually guinea pig or rabbit sera) have been used as source of complement since these are convenient and readily available, showing reproducible activity in sequential tests.

The value of using heterologous mixtures of antiserum and complement has recently been questioned (4) and in this respect, when investigating responses in relation to host immunological reactivity to a developing tumour, a relevant point to resolve is to determine whether or not the host can provide an intact complement system to be activated by syngeneic antibodies to lyse tumour cells. This has been examined in cats, and antibodies from healthy cats exposed to feline leukaemia virus-lysed feline lymphoma cells slowly with cat complement (13). Using this approach it has further been possible to analyse the role of immunosurveillance in this system, in the absence of exogenous factors (13, 14).

In recent reports from this laboratory (11, 12) and others (6), the presence of cytolytic antibodies in the serum of syngeneic rats bearing a transplanted aminoazo dye-induced hepatoma has been described and cytolysis against tumour cells was revealed using guinea pig serum as complement. In the present study, we report the results of analysing whether this antibody killing may be mediated in both in vitro and in vivo tests when rat serum is used as source of complement.

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