Tumor production

Keep, P. A, Searle, F., Begent, R. H. J., Barrat, G. M., Boden, J., Bagshawe, K. D., and Ryman, B. E. (1983). Clearance of injected radioactively labelled antibodies to tumor products by liposome-bound second antibodies, Oncodev. Biol. Med., 4, 273-280. 

The delicate balance maintained by these factors is altered in patients with cancer by two principal mechanisms tumor production of humoral factors that alter calcium metabolism (humoral hypercalcemia) and local osteolytic activity from bone metastases.27 Humoral hypercalcemia causes around 80% of all hypercalcemia cases and is mediated primarily by systemic secretion of parathyroid hormone-related protein... 

Because of high acute toxicity and demonstrated skin tumor production in animals, human contact by all routes should be avoided. ... 

Palmes ED, Orris L, Nelson N Skin irritation and skin tumor production by P-propiolactone (BPL). Am Ind HygJ 23a57-264, 1962... 

Promoter (Carcinogenicity) An agent which increases tumor production by a chemical when applied after exposure to the chemical. 

It is clear that the effects of induction or inhibition of the metabolism will be complex because of the large number of possible metabolic pathways through which benzofalpyrene may be metabolized. For instance, the microsomal enzyme inducer 5,6-benzoflavone inhibits the carcinogenicity of benzofalpyrene in mouse lung and skin, whereas inhibitors such as SKF 525A may increase the tumor production from certain polycyclic hydrocarbons. 

The metabolic activity of various tissues is also a determinant of susceptibility to tumor production. The gastrointestinal tract is resistant to dime thy Ini trosamine carcinogenesis, even when the compound is given orally, as the metabolic activity of this organ is low as far as activation of dimethylnitrosamine is concerned. 

Transformed cells sometimes, but not always, give rise to tumors when injected into an isogenic animal. There may be numerous reasons for the failure to produce tumors on all occasions. One of the best known reasons for lack of tumor production is immunological rejection. The transformed cell resulting from exposure to a tumor virus frequently displays viral antigens which are recognized as for-... 

The first virus linked to tumor production was discovered in 1908 by Ellerman and Bang. Their finding was followed in 1911 by the better known discovery by Peyton Rous of a virus that produces sarcomas in chickens (now known as Rous sarcoma virus, or RSV). Later (1932) Shope showed that a papilloma virus produced cutaneous tumors in rabbits, and Lucke (1934) showed that adenoviruses produced renal adenocarcinoma in the frog. These and other discoveries made in the 1940s and 1950s indicated that exposure to certain viruses could result in tumor production. However, viral oncogenes had not yet been identified, and skeptics... 

Carbazole can be oxidized to the 9-oxyl radical, which has been identified in fish liver it may be related to tumor production. A small number of 9-hydroxycarbazoles has been made. 

Another sign of therapeutic response is a significant decrease in the quantity of a tumor product or marker substance that reflects the amount of tumor in the body. 

It is widely accepted that retinoids inhibit tumor growth and development, or the promotional phase of tumorigenesis (1J5) since it is well known that vitamin A plays a marked, as yet ill-defined, role in controlling the growth and differentiation of epidermis and epidermally-derived structures (16-18). Experimental evidence for this hypothesis rests primarily on the observation that conditions of hypervitaminosis A significantly inhibit tumor production even when initiated after application of the carcinogenic insult. Thus, 13-cis-retinoic acid inhibits the induction of transitional cell... 

In range extrapolations, responses for the same endpoint are inferred outside the range of the data from which the model was derived. These are most commonly used to calculate low-effect concentrations such as the LC10, LC25, or benchmark effect doses or concentrations from the dose-response line (SETAC 1994), or in the case of human health protection to estimate low-risk exposures such as the 10 6 risk of tumor production (USEPA 1995a see Figure 1.4). In the context of acute responses, the model used for extrapolation (the log dose-probit effect Finney 1971) is well tested and widely used. However, the possibility of stimulatory or hormetic... 

The duration for chronic toxicology studies depends on the projected duration of administration to humans (Table 1). The present consensus according to the FDA (5) is that 6-month rodent and nonrodent studies are sufficient for drug candidates intended for long-term human use, provided the candidate is studied in rats, or other appropriate species, to evaluate the potential for tumor production. 

An example of how transport impacts effects on the body can be seen from a consideration of benzo [a] pyrene (BaP). BaP is a polynuclear aromatic hydrocarbon (PAH) that is a component of petroleum and cigarette smoke. It is an established lung carcinogen, but it is BaP s diol-epoxide metabolite that is the actual tumerogen. The path from absorption to tumor production is a five-step process involving two transport steps. The five steps, which are depicted in Fig. 4.1 are ... 

Although pancreatitis, severe injury, and inflammation can all increase its levels, TATI can stfll function as a relatively good tumor marker for various cancers. In most cancers, the increase in TATI is due to tumor production however, inflammation associated with tissue destruction contributes to the overall TATI increase. Serum and urine concentrations correlate well, but because of greater variation in urine, serum is preferred. 

A qualitative test for BTA analytes in urine, termed the BTA stat. test, has been developed. BTA analytes are high molecular weight polypeptides composed of complexes of basement membrane proteins. The presence of BTA analytes in urine is thought to involve either invasion of the basement membrane by tumor, production by the tumor itself, or a combination of these, which maybe linked with the bodjfs immune response. If BTA analytes are present in a significant level, they will combine with latex particles to produce an agglutination reaction, which produces a visible color change on the... 

Direct tumor erosion of the bone Local tumor production of bone-resorbing agents No skeletal involvement (humoral hypercalcemia of malignancy)... 

Rausch, D.M. and S.B. Simpson. In vivo test system for tumor production by cell lines derived from lower vertebrates. In Vitro Cell Dev. Biol. 24 217 - 222, 1988. 

With Potter s development of experimental plasmacytoma in mice, it was established that the turnover of paraprotein (N2), or more simply the serum level (08), was directly related to the weight of solid soft-tissue plasmacytoma. In our laboratory an ascitic form of plasmacytoma has been studied, and using isotope dilution it has been possible to estimate the actual total number of plasmacytoma cells in a mouse. At the same time the serum level of paraprotein was measured and a simple correlation was shown (F2). To the best of my knowledge, this was the first time that the serum level of a tumor product had been directly related to the actually counted number of tumor cells. Incidentally it was noted that the paraprotein could be first detected in the serum, when a 23 g mouse had 3 million tumor cells. 

In conclusion, both coal tar pitch and asphalt produced benign and malignant skin tumors in mice (Niemeier et al. 1988), but C3H/HeJ mice were more susceptible to the formation of malignant tumors than CD-I mice. Concomitant exposure to sunlight reduced tumor production by coal tar pitch, or asphalt, or the combination of coal tar pitch and asphalt compared with nonsolar exposed animals. The... 

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