Host-mediated activity 22

Host-mediated activity of glycoprotein-rich extracts of C. vulgaris strain CK... 

Secondary or procarcinogens, which themselves are inert, must first be activated to ultimate carcinogens by host-mediated enzymatic reactions. The host-mediated activation can be by species-specific enzymes. This explained the previously puzzling observations of certain chemicals being carcinogenic in some species and not in others. 

Plants and microorganisms produce unique and diverse chemical stmctures, some of which act as immunomodulators (18—28). Of specimens used in traditional medicine, approximately 450 plant species have shown antiviral activity out of 4000 plants screened (19). Several tannins (20) exhibit strong inhibition of tumor promotion experimentally. Pretreatment of mice with small amounts of tannins for several days strongly rejected transplanted tumors. This activity has been claimed to be effected through enhancement of host-mediated antitumor activity. 

Simmon VF, Rosenkranz HS, Zeiger E. et al. 1979. Mutagenic activity of chemical carcinogens and related compounds in the intraperitoneal host- mediated assay. J Nat Cancer Inst 62 911-918. 

Monomethylhydrazine-induced mutagenesis was not observed in Ames Salmonella/ microsome with activation (Matheson et al. 1978). In vivo tests in mice (dominant lethal, revertants in host-mediated assay), and dogs (micronuclei) were negative (reviewed in Trochimowicz 1994). However, in vitro chromosomal damage in human and rat tissue has been demonstrated, although in vivo liver DNA damage (as determined by DNA alkaline elution) was equivocal (reviewed in Trochimowicz 1994). 

Host-mediated assay, m the host-mediated assay, target cells cure inoculated into an animal that receives the chemical treatment. The assay can be performed only with cell lines that do not kill and cure not killed by the host. Several chemicals—including AF-2, EMS, DMN, DEN, and MNNG—have been tested in this assay system. These chemicals induce mutations in the direct test or in cell-or microsome-mediated assays. Such studies may be useful in understanding responses—including tissue distribution, activation, detoxification, and elimination of chemicals— in whole animals. 

Metabolic activation systems—such as microsome-, cell-, and host-mediated assays—have been included in mammalian cell mutagenesis systems. Microsome-mediated assays have been used to detect many chemicals, including nitrosamines, polycyclic hydrocarbons, aflatoxins, and vinyl chloride. Cell-mediated assays seem to be a better indicator of in vivo metabolic pathways. Microsome-mediated assays seem suitable for general screening of chemicals, and cell-mediated assays are more valuable in the assessment of data. 

Antiprotozoal (genetically active on S. cerevisiae D7 in the intrasanguineous host-mediated assay) [257]... 

Coriarin A (Scheme 3.97) displays tumour remissive activity owing to host-mediated immunostimulation rather than direct cytotoxirity. The final step of a synthesis of Coriarin A entailed simultaneous hydrogenolysis of seventeen benzyl ethers and four diphenylmethylene acetal groups to give the final target in 80% yield.86... 

In the point-mutation studies (1). Saccharomyces cerevisiae was used as the target cell, and the effects of the chemical were tested in a direct in vitro assay without metabolic activation and in a host-mediated modification. In the direct reverse-mutation assay, there were increases by a factor of 2-6 in the number of His revertants and by a factor of 2-7 in the number of trp revertants over the spontaneous frequencies. In contrast, there were no reported Increases in the number of Hls or trp revertants in the host-mediated assay. 

The most famous example of non-specific polysaccharide immunoadjuvants is lentinan isolated from Lentinus edodes. Since 1985, lentinan has been used as an antitumor agent. Lentinan is a (1 3)-/3-glucop)ranan bearing (1 6)-/3-glucopyranoside branches (O Scheme 1). This neutral polysaccharide suppresses the proliferation of sarcoma 180 tumors implanted subcutaneously in mice. Its antitumor activity was due to a host-mediated reaction with participation of thymus or thymus-dependent cells [1]. The lymphokines induced by this polysaccharide enhance the activity of lymphocytes (e. g., macrophages, helper T cells, and/or natural killer cells) in a dramatic manner [2,3,4,5]. Lentinan-like (1 3)-/3-glucopyranan (schizophyllan) contained in the insoluble fraction of Schizophyllum commune has the stracture shown in O Scheme 2 and is known to possess antitumor activity [6]. 

Interest in host-mediated, antitumor action of noncytotoxic polysaccharides stemmed from dissatisfaction with current cancer chemotherapy experiments. In these experiments, countless numbers of chemical compounds are being tested for their tumoricidal activities, with the aim of attaining a total kill of cancer cells. It has been the experience of clinicians, as well as of laboratory experimenters, however, that successful total kill of cancer cells is apt to include the host too. Hence, the enhancement or potentiation of host resistance emerged as a possible means of inhibiting tumor growth without... 

Some phenothiazines, the so-called half-mustard type, stimulated T-cell blast formation, presented a natural killer cell activity, via possibly the activation of monocytes and macrophages, and an antibody-dependent cellular cytotoxicity of human peripheral blood mononuclear cells, and also showed cytotoxicity against several human cancer cell lines. These phenothiazines also might induce an in vivo antimicrobial activity by possibly their host-mediated immuno-potentiation [146]. Phenothiazines did not demonstrate any apparent mutagenic activity, but they were rather antimutagenic. These data suggest the possible applicability of half-mustard type phenothiazines and benzo[a]phenothiazines to cancer chemotherapy. 

Frezza D, Smith B, Zeiger E. 1983. The intrasanguineous host-mediated assay procedure using Saccharomvces cerevisiae conparison with two other metabolic activation systems. Mutat Res 108 161-168. 

Recently, attention was drawn to a readily accessible bacterial polyglucose A well-defined B-(l- S)-glucan with (DPj ) 540 from cultured Alcali-qenes faecalis var. myxogenes displayed significant host-mediated inhibitory effects against various transplantable tumors. Hydrolytic degradation products (DPn l6) retained some activity. 105... 

Kerklaan P, Bouter S, Mohn G. 1983. Activation of nitrosamines and other carcinogens by mouse-liver S9, mouse hepatocytes and in the host-mediated assay produces different mutagenic responses in Salmonella TA 1535. Mutat Res 110 9-22. 

There are a number of nonspecific laboratory tests that are useful to support the diagnosis of infection. The inflammatory process initiated by an infection sets up a complex of host responses. Activation of complements, such as C3a and C5a, initiates inflammation and sets off a cascade of changes and the subsequent release of mediators, all of which can be measured and monitored. Serum complement concentrations, particularly C3, usually are consumed as part of the host defense mechanism and subsequently are reduced during the early stages of an acute infectious process. Acute-phase reactants, such as the erythrocyte sedimentation rate (ESR) and the C-reactive protein concentration, are elevated in the presence of an inflammatory process but do not confirm the presence of infection because they are often elevated in noninfectious conditions, such as collagen-vascular diseases and arthritis. Large elevations in ESR are associated with infections such as endocarditis, osteomyelitis, and intraabdominal infections. ... 

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