Carcinogen induced tumours

There is much evidence to suggest that carcinogenic N-nitros-amines are metabolised by an oxidative process to produce an alkylating agent (J f2) One potential metabolite is therefore the corresponding N-nitrosamide resulting from 2-electron oxidation at the oc-carbon atom, and, indeed, such compounds appear to induce tumours at the site of application without metabolic activation (3) It follows that the chemical properties of N-nitrosamides are relevant to the etiology of cancer ... 

Tumours induced by chemical carcinogens/irradiation Each tumour usually displays distinct antigen specificity Virally induced tumours Various tumour types display identical tumour-... 

The interest in bile acids as potential carcinogens was subject to investigation as early as 1940 when Cook et al. reported in Nature that repeated injection of deoxycholic acid into the flanks of mice could induce tumour formation in mice." Furthermore, Kelsey and Pienta showed that treatment of hamster embryo cells with lithocholic acid could cause cell transformation. ... 

Brown, K., A. Buchmann and A. Balmain. Carcinogen-induced mutations in the mouse c-Ha-ras gene provide evidence of multiple pathways for tumour progression. Proc. Natl. Acad. Sci. USA 87 538-542, 1990. 

With chemical carcinogens time is also an important factor, both for the appearance of the effect, which may be measured in years, and for the length of exposure. It appears that some carcinogens do not induce tumours after single exposures or after low doses but others do. In some cases, there seems to be a relationship between exposure and dose, that... 

Group II contains the strong carcinogens — substances inducing tumours in a fairly short time in most laboratory animals, the carcinogenic effect on the man being probable (e.g. aminoazo compounds, nitrosoamines). 

Group III includes moderate carcinogens. These are many substances inducing tumours in a smaller fraction of experimental animals (up to 20%) and during their long-term action, i.e. in the second half of the life of these animals. Their carcinogenic effects on the man are still a matter of debate. 

Group IV includes weak carcinogens, which have induced tumours in certain laboratory animals, however, in general the experiments with these substances have so far yielded controversial results. 

The potential protective effect of 2-mercaptoethane sulfonate, which reduces oxidative stress by increasing free thiols in the kidney, on renal toxicity and carcinogenicity induced by ochratoxin A has been examined in a long-term rat study. 2-Mercaptoethane sulfonate significantly reduced karyomegaly but did not reduce the incidence of renal tumours (Pfohl-Leszkowicz Manderville, 2007). 

Although there have been suggestions of causality, there is no definitive evidence of the carcinogenic potential of lead, and lead exposure is not considered to be of concern from this viewpoint. High levels of lead have induced tumours in animals and for this reason alone it has been classified as a possible human carcinogen. However, most studies have found no relationship with cancer but those which have been inconclusive, have concurrent exposure to confounding substances such as arsenic and to smoking. 

Tumours may be induced at various sites in a variety of animals by physical, chemical and viral agents. Chemical induction is the method most frequently used and involves tumour induction by carcinogenic compounds. Thus, 3,4,9,10-dibenzopyrene induces fibrosarcomas in weanling Swiss mice within 10-15 weeks of subcutaneous implantation [17]. Two virally-induced tumours have been used for detecting antitumour activity. These are the Friend leukaemia [18] and Rous sarcoma [19]. The former system is of interest as it is sensitive to a wide spectrum of antitumour agents. 

The main disadvantages of induced tumours for detecting antitumour activity are the difficulties involved in obtaining sufficient numbers of animals for testing at the same time, and the removal of the implanted carcinogen after tumour induction. 

Whilst this prediction of in vivo stability is largely borne out in practice, there is some evidence that other factors are involved and that unexpected degradation mechanisms operate within the body. One of the first observations of degradation of these polymers was made by Oppenheimer" who was working on the carcinogenic properties of plastics. In attempting to elucidate the mechanisms by which plastic films induced tumours after subcutaneous implantation in rodents, certain radiolabelled polymers were employed. " C-labelled polystyrene, polyethylene and poly(methyl methacrylate) were implanted and urine, faeces and respiratory CO2 were monitored for periods over a year. With the polystyrene, nothing radioactive was excreted in the urine until 21 weeks, but some radioactivity was detected after this time. With polyethylene, radioactive species were excreted after 26 weeks and with poly(methyl methacrylate), this occurred after 54 weeks. 

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