A. Lakshma Reddy

Papillomas induced by initiation-promotion differ from those induced by carcinogen alone.

The discovery of a two-stage mechanism of Carcinogenesis in mouse skin, with initiation and promotion as independent components, provided new approaches to the study of the development of neoplasms in experimental animals and humans1–5. However, it is not clear how the carcinogen and promoting agent are involved at different steps in the development of papillomas and carcinomas. Here we have used cell markers in mice to study the mechanism of development of papillomas induced by the classical method of two-stage skin tumorigenesis (initiation with subtumorigenic doses of a carcinogen followed by promotion with phorbol esters) and by multiple treatments with initiating doses of a carcinogen. Our results show that papillomas induced by repeated carcinogen applications arise from significantly more cells than those induced by the carcinogen-promoter regimen.

Integumentary allograft versus autograft reactions inCiona intestinaux: A protochordate species of solitary tunicate

Immunosurveillance or recognition of nonself from self may be regarded as a fundamental characteristic to preserve the integrity of the body in all vertebrates. Recent investigations of immune responsiveness in diverse invertebrates strongly suggest that they also have the ability to recogniz e and react against foreignness in specific ways, comparable to certain vertebrate immune responses (Hildemann and Reddy 1973). Quasi-immunorecognition in the form of allogeneic or intercolony incompatibility is shown by coelenterates (Ivker 1972, Hildemann et al. 1974, Theodor 1969) and colonial tunicates (Bancroft 1903, Mukai, 196%. Oka and Watanabe 1960, Freeman 1970a). Distinct lineages of advanced invertebrates represented by annelids (Cooper 1970, Duprat 1970) and echinoderms (Hildemann and Dix 1972) exhibit primordial cell-mediated immune responses toward allogeneic tissue grafts associated with specialized leukocytes, including lymphocyte-type cells. These specific rejection reactions were found to evoke at least short-term memory. Tunicates belonging to the phylum Protochordata occupy a unique position between advanced invertebrates and true vertebrates. Since many arguments favor the evolution of vertebrates from tunicates (Berill 1955), immunological investigation of this group promises insight into the origins of the elaborate adaptive immune systems of vertebrates. AUogeneic incompatibility or colony specificity is characteristic of all colonial tunicates. In addition, Tanaka and Watanabe (1973) had shown typical nonfusion reactions inBotryllus colonies with destruction of cells in the tunic ofallogeneic colonies. Reaction to foreign bodies, like broken-glass fragments, and mobilization of specialized cell types, like vanadocytes, in encapsulation reactions has been reported in a solitary tunicate Molgula manhattensis (Anderson 1971). But no specificity was observed in encapsulation of autoand allografts transplanted into the branchial sac. These studies are equivocal in the sense that grafts were transplanted to abnormal heterotopic sites.

Micro mixed hemadsorption assay--a sensitive method for detecting antibodies against tumor-associated antigens.

Antibodies against methylcholanthrene (MCA)-induced sarcomas in Fischer (F344) rats were detected by a modified micro mixed hemadsorption (MHA)-assay. The assays detected anti-tumor antibodies as titers up to 1 : 320 in sera from hyperimmunized rats and at titers up to 1 : 160 in sera from rats bearing a 5-8 cm3 progressively growing tumor. MHA-titers decreased when sera were absorbed with sarcoma cells prior to MHA-assays. IgG antibodies in sera from tumor bearing rats showed titers of 1:20 and 1:5. These anti-tumor sera formed rosettes on the corresponding sarcoma cells as well as other sarcomes induced by MCA in F344 and Lewis strain rats tested. The assay was modified for a micro technique using a microtest plate (No. 3034, Falcon, CA). This modification yielded as assay requiring only 10 microliter of test sera. The test is quantitative and highly sensitive and results are reproducible. Several critical factors which influence test results in this assay were examined.