Sarcoma induction

Lloyd RD, Wrenn ME, Taylor GN, et al. 1985. Toxicity of Ra and Th relative to Ra for bone sarcoma induction in beagles. Strahlentherapie [Sonderb] 80 65- 69. 

Spiess FW, Mays CW. 1973. Protraction effect on bone sarcoma induction of Ra 224 in children and adults. In Sanders CL, et al., ed. Radionuclide carcinogenesis. Springfield, VA NTIS, 437-150. 

Sunderman FW, Reid MC, Allpass PR, et al. 1980. Manganese inhibition of sarcoma induction by benzo(a)pyrene in Fischer rats. Proc Am Assoc Cancer Res 21 72. 

The high incidence of sarcomas induced by polysorbate 80, Sodium Patent Blue V and by Sodium Blue VRS is in accord with observations made on the relation between surface activity and the incidence of local sarcomas in long-term injection tests [179,180]. Surface-active food colourings and other additives had been found to produce sarcomas when administered over long periods in concentrated solutions, when the surface tension was below the critical lytic index below which surfactants produce irreversible damage to cells. The physicochemical nature of the toxic action of such surfactants is illustrated by experiments with Sodium Patent Blue V [181] (Fig. 10.22). At 2 % and 3 % levels there was a high incidence of sarcoma induction but at 1 % levels no sarcomas were produced. At 1 % levels the surface tension lowering produces no cell... 

Table 10.17 Physical properties in relation to sarcoma induction (colourings used as sodium salts)...

Gregoire V, Beauduin M, Bruniaux M, et al. Radiosensitization of mouse sarcoma cells by fludarabine (F-ara-A) or gemcitabine (dFdC), two nucleoside analogues, is not mediated by an increased induction or a repair inhibition of DNA double-strand breaks as measured by pulsed-field gel electrophoresis. Int JRadiat Biol 1998 73(5) 511-520. 

Following intravenous injection of Thorotrast in humans and animals, various malignancies were found, primarily liver cancers (latency period of 25-30 years), leukemia (latency period of 20 years), and bone cancers (latency period of about 26 years). Short-lived daughter products of thorium also resulted in the induction of bone sarcoma because of their short radioactive half-lives. Intravenous injection of thorium-228 resulted in dose-dependent induction of bone sarcoma in dogs (Lloyd et al. 1985 Mays et al. 1987 Stover 1981 Wrenn et al. 1986). At the highest administered level, the animals died from systemic radiological effects (e.g., radiation induced blood dyscrasia and nephritis) before the bone sarcoma could develop (Stover 1981 Taylor et al. 1966). A relationship was found between the amount of thorium-227 (half-life of 18.7 days) injected intraperitoneally and the incidence of bone sarcoma in mice (Luz et al. 1985 Muller et al. 1978). 

Anionic polyelectrolytes have been shown to enhance resistance to bacteria and fungi, enhance immune response, inhibit adjuvent arthritis and either depress or stimulate phagocytic activity of the reticuloendothelial system [458,459]. Carboxylic acid polymers have shown interferon induction, antiviral activity, and tumor growth inhibition [460]. The effects include inhibition of sarcoma, leukemia, polyoma and vesicular stomatitis virus. In one application, the cytotoxicity of bleomycin toward cultured mammalian cells was synergisti-cally enhanced by stirring in the presence of high molecular weight polyfacrylic acid) [461]. 

Vincristine has been effectively combined with prednisone for remission induction in acute lymphoblastic leukemia in children. It is also active in various hematologicmalignancies such as Hodgkin s and non-Hodgkin s lymphomas, and multiple myeloma, and in several pediatric tumors including rhabdomyosarcoma, neuroblastoma, Ewing s sarcoma, and Wilms tumor. 

The increased expression of adhesion molecules by the endothelium may activate polymorphonuclear neutrophils (PMN) in rabbits [72], During endotoxic shock, activated PMNs release their granule content and secrete both proinflammatory and cytotoxic molecules. Pickaver et al. [73] were the first to show PMN cytotoxicity against tumor cells. We showed that PMNs are toxic for PROb colon tumor cells [74] in BDEX rats. In vivo, PMNs have been implicated in the Schwartzman reaction [75], and may be involved in LPS-induced tumor necrosis. PMNs, when activated by LPS, synthesize and release NO. The role of NO in tumor growth will be discussed later. The decrease in tumor growth after intradermal injections of LPS is attributed to the induction of TNF-a secretion by PMNs both in intradermal tumors (Meth A sarcoma in BALB/c mice, MH-134 hepatoma in C3H/He mice, Lewis Lung carcinomas in C57BL/6 mice) and pulmonary Meth A metastases [76,77],... 

As is implied by its name, the first TNF-a-dependent mechanism described was the induction of tumor necrosis in vivo through its role in tumor vasculature. However the mechanisms of the in vitro toxicity of TNF-a to tumor cells imply apoptosis rather than necrosis [97], Tumor necrosis in SCID (severe combined immuno-deficiency) mice treated with LPS does not lead to the rejection of tumors [98], Furthermore, necrosis and tumor regression must be dissociated since anti-IFN-y antibodies inhibit LPS-induced regression of Meth A sarcoma in mice, but not the necrotic hemorrhage attributed to TNF-a. It is now accepted that the antitumoral effect of TNF-a is indirect and dependent on acquired immune response. Matsumoto et al. [99] reported that, while TNF-a itself has no effect on hepatoma KDH-8 tumor cells in vitro, the antitumoral effect of the lipid A ONO-4007 against KDH-8 tumors in vivo is inhibited by anti-TNF-a antibodies in WKAH rat, showing an indirect effect of TNF-a. 

Two groups of 36 and 40 female C3HA mice (a strain resistant to 1,2-dimethylhydrazine induction of uterine sarcomas), 2-3 months of age, received 20 weekly sub-... 

Phenanthroline has antitumor properties against sarcoma in mice374 and inhibits induction of carcinoma in rats.396 Quaternary salts of 6-methyl-1,10-phenanthroline are also carcinostatic.397... 

Chronic infections such as HIV result in immunosuppression as a result of induction of CD4+ Treg cells. Increased risk of Kaposi s sarcoma, non-Hodgkin s lymphoma and liver cancer is associated with long-term infections such as HIV. Immunosuppression in HIV-infected individuals occurs before the development of AIDS, which proceeds before the depletion of CD4+ T cells, and the induction of Treg cells may play a role in this process. The mechanisms are IL-10-independent and include the involvement of TGF-(3 secreted via signaling through cell-cell interaction involving CTLA-4. 

De Jong M, Coppee MC, De Halleux F, Deckers C, Maisin H. Immunosuppression and carcinogenesis effects of azathioprine on induction of sarcomas by 3-methylcholanthrene. Neoplasma 1977 24 139-46. 

Evdokiou, A., Labrinidis, A., Bouralexis, S., Hay, S., and Findlay, D.M. (2003). Induction of cell death of human osteogenic sarcoma cells by zoledronic acid resembles anoikis. Bone 33 216-228. 

Perhaps the first to be recognized in toxicology concerned the induction of sarcomas following the local injection of chemicals subcutaneously in rats. Although there can be little doubt that the injection of small quantities of chemicals such as 7,12-dimethylbenz(d )anthracene actually induces these tumors, overloading the tissues with dyestuffs may well lead to cancer because of a mechanism dependent on factors other than the specific interactions of the test chemical. 

In mice, skin application leads rather quickly to carcinoma formation. Subcutaneous injection produces sarcomas in rats or mice. Oral administration in sesame oil to female Sprague-Dawley rats results in rapid induction of breast cancer, while oral administration to mice during the last week of pregnancy produced a threefold increase in incidence of tumors. The most common types were lymphoma and lung tumors. 3-MC has reportedly produced skin tumors in mice, injection site tumors in rats, large... 

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