Precancerous lesions

Actinic keratoses are the most common epithelial precancerous lesions which occur primarily on sun-exposed skin of middle-aged and elderly people as multiple erythematous macules or papules with a dry adherent scale (Figs. 12.1, 12.2 and 12.3). 

Wellings SR, Jensen HM, Marcum RG (1975) An atlas of subgross pathology of 16 human breasts with special reference to possible precancerous lesions. J Natl Cancer Inst 55 231-275... 

Other types of studies summarized include experiments in which the agent or mixtme was administered in conjunction with known carcinogens or factors that modify carcinogenic effects studies in which the end-point was not cancer but a defined precancerous lesion and experiments on the carcinogenicity of known metabolites and derivatives. 

Yim SH, Ward JM, Dragan Y et al. Microarray analysis using amplified mRNA from laser capture microdissection of microscopic hepatocellular precancerous lesions and frozen hepatocellular carcinomas reveals unique and consistent gene expression profiles. Toxicol Pathol 2003-,31 295-303. 

Skin cancer is the most common type of cancer. Damage to skin DNA from sunlight is the most common cause of skin cancer. This causes mutations that result in formation of cancer cells and that suppress the immune responses that normally prevent replication of such cells. The class of chemicals most commonly associated with causing skin cancer are the polycyclic aromatic hydrocarbons from sources such as coal tar. These can be metabolized to electrophilic substances that bind with DNA to initiate cancer (see Figures 7.3 and 8.3). Arsenic in drinking water has been established as a cause of precancerous lesions, called arsenical keratoses, and squamous cell carcinoma of skin. 

Krishnaswamy K, Prasad MR Krishna TR et al. A case study of nutrient intervention of oral precancerous lesions in India. Eur J Cancer oral Oncol 1995 3 1 41 -48. 

No studies were located regarding cancer in humans after dermal exposure to barium. Dysplasia of the cervical epithelium was reportedly induced in a woman who had a barium chloride solution applied to her cervix (Ayre 1966). The use of dimethyl sulfoxide in combination with the barium chloride solution reportedly enhanced the ability of barium chloride to induce dysplasia. Dysplasia can be regarded as a potential precancerous lesion. The significance of the observations reported in this study are difficult to assess, since only one subject was exposed and because there have been no reports of similar findings in other human or animal studies. Also, the vehicle used was not specified in this study. 

However, despite the firm experimental basis and encouraging clinical studies, prophylaxis with NSAIDs to prevent colon cancer in patients who have polyps or in the population in general is notjustified because of the GI toxicity of such therapy. With the introduction of Cox-2 inhibitors, it now is feasible to test the hypothesis that inhibition of Cox-2 over prolonged periods of time would be protective against the development of colon polyps. Since it is well accepted that colon polyps are precancerous lesions, the prevention of polyps should translate into a reduction in the incidence of colon cancer. 

A needed for normal vision, reproduction, and maintenance of healthy skin, mucous membranes, bones, red blood cells, cell differentiation, and im-mune fimction night blindness, xerophthalmia, loss of appetite, increased susceptibiHty to infections, skin disorders, poor growth, defective reproduction regression of precancerous lesions, reduces measle-associated morbidity in children... 

E lipid-soluble antioxidant, prevents lipid oxidation of membranes, needed for healthy blood cells and tissues, blocks nitrosamine formation, protects PUFAs from autoxidation, important for normal immune fimction neuromuscular disorders, red blood ceU mpture (both uncommon) reduces risk of chronic disease (cardio-vascular, precancerous lesions, cancer), immunoenhancement, protec-tion from exercise-induced muscle injury, improves metaboHc control, re-duces risk of compHcations in diabetes... 

Monitoring of the levels of total sialic acid and lipid-associated sialic acid in serum is an important diagnostic tool for the detection of precancerous lesions [224], Transition-state analogues derived from sialic acid are potent inhibitors of sialidases from various influenza virus strains, and these have been evaluated clinically as influenza remedies [225], A detailed review of our current knowledge regarding the occurrence, specificity and function of sialic acid-specific lectins, particularly those that occur in viruses, bacteria and non-vertebrate eukaryotes has been recently published [226],... 

Chronic exposure to PAHs can produce a variety of effects. Exposure to the eyes can result in irritation and photosensitivity. Dermal exposure can result in erythema, burns, and coal tar warts (precancerous lesions enhanced by ultraviolet light exposure). Inhalation exposure may cause irritation to the respiratory tract accompanied by cough and bronchitis. Oral exposure may produce a thickening and/or whitening of the oral mucous membranes. In addition to the local effects at the site of entry, systemic toxicity may occur, which could result in hepatic or renal effects. Some PAH compounds have been noted to cause hematological effects (anemia, leukopenia, and pancytopenia) in animals and suppression of selective components of the immune system. 

Chronic exposure to 3-MC can result in irritation, chronic cough, bronchitis, and bronchogenic cancer. Leukoplakia and cancers of the lip and oral cavity can develop. Dermal contact has been associated with precancerous lesions called coal tar warts which are enhanced by exposure to UV light. Erythema, dermal burns, acneiform lesions, photosensitization and cancer may develop upon chronic exposure. 

There is very limited evidence for CYP expression in the human stomach. Furthermore, it is difficult to propose any function for gastric CYPs because the gastric epithelium secretes rather than absorbs. However, the potential of those CYPs expressed in the stomach to play roles in stomach cancer has been investigated in cases of intestinal metaplasia of the stomach. Intestinal metaplasia of the stomach, which involves the replacement of the gastric mucosa with a small intestine-like epithelium (100), is considered to be a precancerous lesion (101). A combination... 

No tumors or precancerous lesions were reported in rats administered 0.04-66.0 mg Hg/kg/day as phenylmercuric acetate in the diet for 2 years (Fitzhugh et al. 1950). As discussed above for mercuric acetate, no conclusions can be drawn from this study because of its limitations. 

In a 2-year oral chronic-duration feeding study, no tumors or precancerous lesions were noted in rats administered mercuric acetate in the diet at doses of 0.2-66 mg Hg/kg/day (Fitzhugh et al. 1950) no conclusions could be derived on the carcinogenicity of mercuric acetate. The study was limited because the group sizes were small (10-12 rats per group) survival data were not reported a considerable but unspecified number of rats reportedly died from pneumonia, which reduced the sensitivity of the study to detect a carcinogenic response and only limited histopathological analyses were performed. 

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