Tissue-specific resistance to cancer development in the rat: phenotypes of tumor-modifier genes

• Published in: Carcinogenesis (New York) Vol. 23; no. 1; pp. 1 - 9
• Main Authors: Wood, Geoffrey A., Korkola, James E., Archer, Michael C.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-01-2002
• Subjects: 2-AAF; 2-acetylaminofluorene; 3′-dimethylaminoazobenzene; 3′-Me-DAB; Animals; Berlin–Druckrey; Biological and medical sciences; Brown Norway; Buff; Buffalo; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cop; Copenhagen; CTL; cytotoxic T-cells; DEN; diethylnitrosamine; dimethylbenz[a]anthracene; DMBA; ENU; ethylnitrosourea; F344; Fischer F344; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease - genetics; Genotype; glutathione S-transferase; GST; ha-ras gene; hepatocyte growth factor; HGF; Humans; IDP; intraductal proliferation; Liver Neoplasms - genetics; Long–Evans; major histocompatability complex; Mammary Neoplasms, Animal - genetics; matrix metalloproteinase; methylnitrosourea; MHC; MMP; MNU; Molecular and cellular biology; natural killer; Neoplasms - genetics; neu gene; Oncogenes - genetics; Organ Specificity - genetics; partial hepatectomy; peripheral nervous system; Peripheral Nervous System Neoplasms - genetics; Phenotype; PNS; Rats; resistant hepatocyte; SHR; spontaneously hypertensive rat; Sprague–Dawley; triiodothyronine; Wistar–Furth; Wistar–Kyoto; Peripheral nervous system; Nervous system diseases; Premalignant lesion; Rat; Liver; Rodentia; Tissue specificity; Hepatic disease; Modifier gene; Malignant tumor; Peripheral neuropathy; Cell differentiation; Carcinogenesis; Resistance; Mammary gland diseases; Vertebrata; Phenotype; Mammalia; Animal; Digestive diseases; Mammary gland; Mechanism of action; Tumor cell
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/23.1.1

Resistance to carcinogenesis in the rat is both strain- and tissue-specific. The phenotypic characteristics of resistance in the mammary gland, liver and peripheral nervous system (PNS) are strikingly similar. In all three tissues, initiation is intact with subsequent formation of preneoplastic cells and lesions. In the mammary gland and PNS, activation of the Ha-ras and neu proto-oncogenes, respectively, takes place. A number of different modifier genes are involved in resistance, many of which appear to be tissue-specific in their action with no overlap between strains. A single resistance phenotype, however, involving the formation, growth and subsequent loss of preneoplastic lesions is common to all three tissues of resistant strains. In the PNS, there is evidence that preneoplastic cells are eliminated by apoptosis or immunosurveillance. In the mammary gland and liver, the immune system is not involved in the loss of preneoplastic lesions and there are no clear differences between susceptible and resistant strains in the kinetics of proliferation and apoptosis of preneoplastic cells. The evidence to date favors a mechanism in which preneoplastic cells from these tissues undergo a process of remodeling/redifferentiation to yield cells with a normal phenotype. Identification of human homologues of rodent tumormodifier genes will result in a better understanding of cancer development and potentially provide new strategies for prevention and therapy.