Spontaneous and Induced Tumors in Germ-Free Animals: A General Review

Abstract

Cancer, bacteria, and immunity relationships are much-debated topics in the last decade. Microbiome's importance for metabolic and immunologic modulation of the organism adaptation and responses has become progressively evident, and models to study these relationships, especially about carcinogenesis, have acquired primary importance. The availability of germ-free (GF) animals, i.e., animals born and maintained under completely sterile conditions avoiding the microbiome development offers a unique tool to investigate the role that bacteria can have in carcinogenesis and tumor development. The comparison between GF animals with the conventional (CV) counterpart with microbiome can help to evidence conditions and mechanisms directly involving bacterial activities in the modulation of carcinogenesis processes. Here, we review the literature about spontaneous cancer and cancer modeling in GF animals since the early studies, trying to offer a practical overview on the argument.

Keywords: colorectal cancer; germ-free animals; induced tumors; microbiome; spontaneous tumors.

Figure 1

AOM-induced CRC in rat. AOM is an azide compound, active derivative of DMH and induces genetic damage in the colon cells. The carcinogen promotes classical colon carcinogenesis events with adenomas to carcinoma progression [56]. (A) aberrant crypts with (B) overexpression of p21 k-ras protein (dark brown) and (C) development of infiltrating adenocarcinoma after 32 weeks from the induction (original microphotographs from Luca Vannucci’s Lab archive).