Chronic Trypanosoma cruzi infection associated with low incidence of 1,2-dimethylhydrazine-induced colon cancer in rats

Abstract

Experimental data have demonstrated that chronic infection with intracellular parasites may enhance resistance against some types of tumour. This phenomenon has not yet been demonstrated for experimental Trypanosoma cruzi chronic infection. This study investigated the effect of a specific colon cancer inducing drug, 1,2-dimethylhydrazine (DMH), on chronically T.cruzi infected Wistar rats. Infection was obtained by inoculation of 10(5) tripomastigote forms by subcutaneous (s.c.) route. Acute phase of the infection was monitored every other day by examination of a blood smear from each animal until negativation. In the early chronic phase of the infection, colon adenocarcinoma was induced by weekly s.c. injections of DMH at a dose of 20 mg/kg body weight for 12 weeks. 102 animals were divided in four test groups: 39 infected rats received DMH (group 1); 32 non-infected rats received DMH (group 2); 16 infected rats and 15 non-infected animals were used as control groups. Animals were killed 6 months after the first dose of DMH. The whole colon was removed and prepared for light microscopic examination. Twelve animals from group 1 and 22 from group 2 had colon adenocarcinomas, the proportion of cancer being 30.7 and 68.7%, respectively (chi(2) = 10.16; P < 0.05). The relative risk of having a colon tumor in infected animals (group 1) was 0.45 (IC 95% 0.26-0.76), which is a protective risk compared with non-infected animals. These findings show that chronic infection with T.cruzi is associated with a lower incidence of DMH-induced colon cancer in rats.

Infection and Cancer: Revaluation of the Hygiene Hypothesis

“…13,28,55]; more specifically, BCG, vaccinia, or yellow fever virus vaccinations have been linked to melanoma protection (56,57). In addition, infectious agents have also been inversely associated with cancer (Table 1), as in the case of Trypanosoma cruzi, which can result in lower incidence of experimentally induced rodent colon cancer (58). These observations support the protective action of infections, as proposed by the hygiene hypothesis (11)(12)(13)(14).…”

Trypanosoma cruzi infection and/or administration of the nonsteroidal anti-inflammatory nimesulide increase the number of colonic crypts overexpressing metallothioneins in rat colon carcinogenesis

“…It has been known for decades that Trypanosoma cruzi infection has an anticancer effect (1) and we have provided evidence showing that chronic infection with T. cruzi reduces the incidence of 1,2-dimethylhydrazine-induced colorectal tumors (2). Available clinical data strongly suggest the existence of protection against colon cancer in patients with megacolon due to Chagas' disease, which is caused by T. cruzi (3).…”

“…The infection was monitored by checking the parasitemia 5 days after infection by light microscopic examination of a blood smear (2). The animals were treated with one weekly subcutaneous dose of 12 mg/kg DMH for 4 weeks.…”

Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen

“…The sections were incubated for 1 h at 37°C in a humidified chamber with mouse monoclonal anti-ß-catenin antibody (IgG1; Transduction Laboratories, Lexington, KY, USA) diluted 1:2000 in a blocking solution. To estimate colonic cell proliferation, thin slices (4 mm) from the paraffin-embedded colon of all animals were Denervation inhibits aberrant crypt foci in the rat colon www.bjournal.com.br immunostained with anticyclin/PCNA antibody (PCNA/Novocastra, Newcaste-upon-Tyne, UK), diluted 1:2000 in a blocking solution (5).…”