Tumours development

FUTAKUCHI M, HIROSE M, MIKI T, TANAKA H, OZAKI M and SHIRAI T (1998) Inhlhition of DMBA-initiated rat mammary tumour development hy l-O-hexyl-2,3,5-trimethylhydroquinone, phenylethyl isothiocyanate, and novel synthetic ascorbic acid derivatives , Eur J Cancer Prev, 7 153-9. 

IARC. 1989. Tumour development following internal exposures to radionuclides during perinatal period. Richland, WA International Agency for Research on Cancer. 

As well as providing fuel, butyrate (which contains four carbon atoms) can reduce the proliferation of colonocytes, which may reduce the risk of tumour development. This is one suggestion to explain how high-fibre diets protect against colon cancer (Chapter 21). 

Failure to control the rate of degradation of cyclins could lead to their over-expression, increasing the risk of tumour development. 

The relationship between aU three definitions can also be interpreted as a linear sequence of events from binding to the receptor through to the whole-body response (Figure 12.3). The sequence has some similarities to that which is initiated by a growth factor for example control of proliferation end tumour development (Chapter 21 (see Figure 21.3)). 

It is tempting to suggest that the binding of Ras and Raf to membranes may provide a link between diet and tumour development. There is evidence that a chronic alteration in the phospholipid composition of membranes, which can be... 

A viral infection that results in insertion of viral DNA adjacent to a proto-oncogene will be a rare event, so that the risk of tumour development will be very low. In con-... 

Figure 21.10 Modifications by which proto-oncogenes can be activated. Conversion to an oncogene or excess activation of proto-oncogene results in excess growth-promoting activity, and consequently increases the risk of tumour development (see text). Process (iv) can result in many cells in the host being infected with an oncogene that has been formed from a protooncogene within the virus.

Intense research has revealed much about the molecular mechanisms involved in tumour development but much less is known about the metabolic changes in cancer. Nonetheless, most deaths from cancer are caused not directly by the tumour but by infections due to an immune system that has been impaired by metabolic disturbances in the whole... 

R. K. Wall, D. Stoiber, L. Nguyen, J. Hart, M. D. Sitrin, T. Brasitus and M. Bissonnette, Ursodeoxycholic acid inhibits the initiation and postinitiation phases of azoxymethane-induced colonic tumour development. Cancer Epidemiol. Biomarkers Prev., 2002, 11, 1316. 

In one inhalation study in rats, 1,3-butadiene increased the incidence of tumours at several sites. The tumour increases were mainly in organs in which tumours develop spontaneously. The response was seen mainly at 8000 ppm [17 700 mg/m ]. 

Mouse. A group of 20 female SEN mice, four weeks of age, was treated twice weekly for 51 weeks with 0.2 mL of a 100 mg/mL solution of benzoyl peroxide in acetone applied to the skin shaved 48 h previously. A group of 15 mice receiving 0.2 mL acetone served as controls. At the termination of the experiment, there were no skin tumours among the control mice, compared with 8/20 in the benzoyl peroxide-treated mice Ip < 0.05), of which 5/20 were squamous-cell carcinomas. The first tumour developed in week 24. Six of 20 mice showed epidermal hyperplasia (Kurokawa et al., 1984). 

Benzal chloride was tested in two experiments in mice by skin application, the results of which were reported together. In the first experiment, the total dose of benzal chloride was about 289 mg per mouse during a 50-wcek dosing period, after which all mice were killed at week 82. No skin tumours developed in 20 controls, while, in the treated group of 19 (14 of which had died by the end of the experiment), nine mice had squamous cell carcinomas of the skin and two had skin fibrosarcomas. In the other experiment in which the total benzal chloride dose was about 1109 mg per mouse, but which was terminated after just 43 weeks, 2/10 mice developed skin papillomas compared with 0/10 in the controls (lARC, 1982). 

Rat. Four groups of 120 male and 120 female Sprague-Dawley rats were exposed to 0 (control), 50,400 and 4000 ppb [0, 0.37,2.9 and 29 mg/m- ] hexamethylphosphoramide vapour for 6 h per day on five days per week for periods ranging from nine months to two years. In an additional study, four groups of 100 male and 100 female rats were similarly exposed to 0, 10, 50 and 100 ppb [0, 73, 370 and 730 pg/m ] atmospheres. Nasal tumours were first found after approximately seven months of exposure at 400 and 4000 ppb, after nine months at 100 ppb and after 12 months at 50 ppb. No exposure-related tumours were found at 10 ppb. Tumour incidences at 24 months were 50 ppb, 15% (12 months of exposure) and 25% (24 months of exposure) 100 ppb, 19% (six months of exposure) and 56% (13 months of exposure) 400 ppb, 82% (10 months of exposure) 4000 ppb, 83% (nine months of exposure). Most tumours developed in the squamous or respiratory epithelium and nasal glands, all of which showed squamous metaplasia or dysplasia in the anterior nasal cavity. Exposure concentrations correlated with tumour incidence and latency, but not with tumour type. The total of 473 nasal tumours included 72% epidermoid carcinomas, 15% adenoid squamous carcinomas and 8% papillomas. Most tumours (59%) developed in the anterior nasal cavity and then progressed to the posterior nasal cavity (41%) (Lee Trochimowicz, 1982a). 

S100A4 Overexpression Enhanced tumour development and metastasis Increased right ventricular systolic pressure, right ventricular hypertrophy, reduced ventricular elastance and decreased cardiac output. 

Knock-out Tumour development and reduced apoptosis Delayed tumour uptake, decreased tumour incidences, no metastasis after transplantation of highly metastatic mammary carcinomas. Enhanced astrocyte migration after demyelination... 

Shoham J, Inbar M, Sachs L. Differential toxicity on normal transformed cells in-vitro and inhibition of tumour development in-vivo by concanavalin-A. Nature 1970, 227, 1244-1246. 

The use of hormonal contraceptives for eight years or more has led to a 4.4-fold increased risk of hepatocellular carcinoma [24]. Snch tumours develop in non-cirrhotic livers, and it has been found that they metastasise rarely and do not infiltrate [16]. There are limited data specifically on POCs. Results from a WHO study provided no evidence that use of DMPA altered the risk of developing liver cancer, but the power of the study to detect small alterations in risk was low [5]. 

Harvey, M., Vogel, 11 Morris, D., Bradley, A Bernstein, A and Donehower, L. A. (1995). A mutant p53 transgene accelerates tumour development in heterozygous but not nuUizygous p53-deficient mice. Nature Cenet. 9,305-311. 

Aristolochic acid and its salts, originated from a weed, Aristolochia clematitis, have toxic and carcinogenic effects to the kidneys and urothelium [45], respectively. Ivic [46] postulated that this plant may be a cause of Balkan nephropathy, but failed to provide convincing evidence from field surveys. Evidence that A. clematitis played a central role in the etiology of Chinese herb nephropathy [47-49], a condition similar to Balkan nephropathy, initiated a second look at this previously abandoned hypothesis and it gained a lot of weight by recent data on the association between DNA adduct formation derived from AA, mutation pattern and tumour development in BEN [50] (see also chapter 33). 

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