Tumorigenesis

Chronic Toxicity Studies. With the exception of tumorigenesis, most types of repeated exposure toxicity are detected by subchronic exposure conditions. Therefore, chronic exposure conditions are usually conducted for the following reasons if there is a need to investigate the tumorigenic potential of a material if it is necessary to determine a no-effects or threshold level of toxicity for lifetime exposure to a material and if there is reason to suspect that particular forms of toxicity are exhibited only under chronic exposure conditions. 

For the above reasons, chronic exposure studies are frequently designed in such a way that it is possible to combine observations for tumorigenesis and noimeoplastic tissue injury. Chronic studies are usually extensively monitored. It is common practice to sacrifice animals at intervals during the study in order to detect the onset of any tissue injury. For two-year exposure studies, it is most meaningful to have interim sacrifices at 12 and 18 months. 

Many anticancer agents currently in use, including chemotherapeutic drugs and radiation, are potent inducers of apoptosis and cell-cycle arrest. It is believed that induction of these molecular pathways is central to the efficacy of such agents [1]. Genetic and epigenetic alterations that contribute to tumorigenesis... 

Zornig M, Hueber A, Baum W et al (2001) Apoptosis regulators and their role in tumorigenesis. Biochim Biophys Acta 1551 1-37... 

Marlowe, J.L. and Puga, A. (2005). Aryl hydrocarbon receptor, cell cycle regulation, toxicity, and tumorigenesis. Journal of Cellular Biochemistry 96, 1174-1184. 

Schuller U, Kho AT, Zhao Q, Ma Q, Rowitch DH (2006) Cerebellar transcriptome reveals cell-type and stage-specific expression during postnatal development and tumorigenesis. Mol CeU... 

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CHUNG F L, KELLOFF G, STEELE V, PITTMAN B, ZANG E, JIAO D, RIGOTTY J, CHOI C I and RiVENSON A (1996) Chemopreventive efficacy of arylalkyl isothrocyanates and N-acetylcysteine for lung tumorigenesis in Fischer rats . Cancer Res, 56 772-8. 

ZHOU J R, MUKHERJEE P, GUGGER E T, TANAKA T, BLACKBURN G L, CLINTON S K (1998) Inhibition of murine bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis and angiogenesis. Cancer. Res. 58 5231-8. 

MORSE M A, KRESTY L A, STEELE V E, KELLOFF G J, BOONE C W, BALENTINE D A, HARBOWY M E and STONER G D (1997) Effects of theaflavins on N-nitrosomethybenzylamine-induced esophageal tumorigenesis , Nutr Cancer, 29 (1), 7-12. 

Aziz, R.M. et al., The effect of freeze-dried blueberries on N-nitrosomethylbenzy-lamine tumorigenesis in the rat esophagus, Pharmaceut. Biol. 40 (Suppl.), 43, 2002. 

Kresty, L.A. et al., Chemoprevention of esophageal tumorigenesis by dietary administration of lyophilized black raspberries. Cancer Res., 61, 6112, 2001. 

Siegers, C.P., Bumann, D., Trepkau, H.D., Schadwinkel, B. and Bareytton, G. (1992). Influence of dietary iron overload on cell proliferation and intestinal tumorigenesis in mice. Cancer Lett. 65, 245-249. 

Additional genes and protein receptors are believed to be important in colorectal tumorigenesis. Cyclooxygenase 2 (COX-2), which is induced in colorectal cancer cells, influences apoptosis and other cellular functions in colon cells, and overexpression of the epidermal growth factor receptor (EGFR), a transmembrane glycoprotein involved... 

Richmond A, Fan GH, Dhawan P, Yang J. How do chemokine/chemokine receptor activations affect tumorigenesis Novartis Found Symp 2004 256 74-89. 

Arenberg DA, Kunkel SL, Polverini PJ, Glass M, Burdick MD, Stricter RM. Inhibition of interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice. J Clin Invest 1996 97(12) 2792-2802. 

Zou H, McGarry TJ, Bernal T, Kirschner MW 1999 Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science 285 418-422... 

Lian, F., D. E. Smith, H. Ernst, R. M. Russell, and X. D. Wang. 2007. Apo-lO -lycopenoic acid inhibits lung cancer cell growth in vitro, and suppresses lung tumorigenesis in the A/J mouse model in vivo. Carcinogenesis 28(7) 1567-1574. 

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