Arsenic experimental animals

Exposure to arsenic has been associated with different types of human cancers such as respiratory cancers and epidermoid carcinomas of the skin, as well as precancerous dermal keratosis. The epidemiological evidence of human carcinogenicity is supported by carcinogenesis in experimental animals (Deknudt et al. 1986). 

All known human carcinogens - the substances ranked by lARC as having been causally linked to human cancers - have been shown to be capable of inducing cancers in some (but not all) species of experimental animals, with the possible exception of arsenic. Arsenic is a human carcinogen, however it has not been adequately tested in animals - so it is perhaps not a real exception to the rule. A few examples of carcinogens that are known to be active in both humans and animals are presented in Table 6.4. 

There is limited evidence of carcinogenicity in experimental animals. However, in one report arsenic administered for 2 years in the drinking water of female mice was associated with an increased incidence in tumors involving lung, liver, gastrointestinal tract, and skin. ... 

Exposure to retinoic acid, methylnitrosourea, and clomiphene during the early embryonic period, prior to the induction of the neural plate (before day 18 in the human), results in an increased incidence of neural tube defects and other malformations in experimental animal models (Bennett Finnell, 1998). In addition, exposure of rodents to teratogens such as retinoic acid, arsenic, and valproic acid during the period of neurulation results in neural tube defects such as spina bifida and encephaloceles (Adams Lammer, 1993 Bennett Finnell, 1998). Of these, therapeutic use of... 

Santra, A., Maiti, A., Das, S., Lahiri, S., Chakraborty, S.K., Guha Mazumder, D.N. (2000). Hepatic damage caused by chronic arsenic toxicity in experimental animals. Clin. Toxicol. 38 395 05. 

Unexpected findings with animal feeds poor in inorganic arsenic and speculation of the possible essentiality of arsenic due to its position in the Periodic Table below phosphorus and next to selenium (both of which are known for their essential properties), led to the initiation of plans to study arsenic deficiency in experimental animals. Some earlier experiments, however, were unsuccessful as initially it was impossible to prepare correct arsenic-deficient diets. This was later achieved by Anke and coworkers (Anke et al. 1976a, b, 1987, 1990, 2001) in studies with goats and minipigs, and by researchers of the U S Department of Agriculture with rats, chicks and hamsters (Nielsen et al. 1975 cited in Uthus 1992, and reviewed by Uthus 1992, 1994, and Nielsen... 

Metals Induce Cancer When Administered to Experimental Animals. Again, the reader is referred to many recent comprehensive reviews which discuss the evidence that certain metals cause cancer in experimental animals (9,10,J1). The most credible data implicates cadmium, chromium, co 6 a TT, and nickel as carcinogens in experimental animals. It should be noted that while arsenic has been shown to be responsible for the induction of human cancer, attempts to induce cancer in experimental animals with arsenic and its compounds have not been successful. In contrast, while cobalt induced cancer in experimental animals, numerous epidemiological studies have failed to show a correlation between excessive human exposure to cobalt and the induction of human neoplasia. One of the most studied metal carcinogens are the nickel compounds, of which crystalline Ni3 2 appears to be the most potent (1,2,12). Ni3 2 has been shown to induce cancer at... 

Endothelial cells containing large foamy vacuoles were described in a case of Morquio s disease (WissE et al. 1974). Neoplastic lesions of endothelial cells, angiosarcomas, have been noted in human liver and in experimental animals. Several toxic environmental agents, such as vinyl chloride, arsenic, and thorotrast, have been impUcated in the pathogenesis of these lesions (Popper et al. 1978). 

The results allow a tentative extrapolation of the arsenic adequacy of experimental animal diets. Those containing 2 ng/g arsenic are clearly deficient for minipigs, goats, and chicken, whereas diets containing 350 ng/g arsenic prevent deficiencies in minipigs and goats. 

Ultra trace elements Normally comprising less than 1 p,g/g (less than 0.0001% by weight) possible ultra trace elements in humans include the metalloids boron (B) and silicon (Si), the halogen fluorine (F), metalloid arsenic (As) and the transition metal vanadium (V) other possible ultra trace elements in other organisms include the alkali metal lithium (Li), halogens fluorine (F) and bromine (Br), transition metals cadmium (Cd) and tungsten, also known as wolfram, (W) and post-transition metals lead (Pb) and tin (Sn). Despite demonstrations of their roles in experimental animals, the exact function of these elements in human tissues and their importance for human health are uncertain. 

In metabolic studies with animals it is often difficult to distinguish between processes carried out by the animal and those performed by resident microorganisms, such as the gut microflora. In the following, the transformations refer to those taking place within the marine animal, whether microbially mediated or otherwise. Metabolic studies with marine animals are faced with further complications because water can be an important uptake route. A chemical, in this instance arsenic in its various forms, may undergo microbial conversions in the water, and the resultant metabolites may be accumulated by the marine animal. Thus, careful experimentation may be required to determine what is occurring inside rather than outside the animal. 

Humans concluded that there was sufficient evidence for the carcinogenicity of soluble calcium chromate and several relatively insoluble hexavalent chromium compounds in laboratory animals. Tumors were mainly induced at the administration site. In addition, experimental exposure to Be, Cd, Ni, and Sb has caused lung tumors in rats, while various beryllium compounds produced osteosarcomas in rabbits by implantation or injection (Hayes 1997). Rossman et al. (2001) could show a co-carcinogenic action of arsenic with solar UV radiation on mouse skin. Apparently strain as well as species differences of the susceptibility to the action of metals may cause variable outcome of carcinogenicity tests for example, in mice this is caused by higher metallo-thionein levels (Oberdorster et al. 1994, Waalkes and Rehm 1994). 

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