Non-neoplastic

Obermuller-Jevic et al. (2003) comparison PrEC-non-neoplastic cells M -trans/5% cis isomers 0.5—5.0pM THF affected cell cycle, corrected for THF alone values 48 h medium changed every 24 h Lycopene uptake 3H thymidine incorporation for proliferation... 

Since HU needs to be taken lifelong in the treatment of non-neoplastic conditions such as SCA (since the inhibition of ribonucleotide reductase is reversible) a major concern is its long term secondary effects. Several studies have shown the potential leukomegenic effect of HU in myeloproliferative disorders [22], [23]. Such concern becomes quite legitimate in sickle cell patients with permanently expanded erythropoiesis in whom the use of HU is at the limit of marrow toxicity. Hence alternative therapies must be sought for. 

In humans, epithelial cells of the flat non-neoplastic colonic mucosa of individuals with colon cancer often have reduced capacity to undergo DOC-induced... 

Additionally, two studies have measured colorectal epithelial cell proliferation and apoptosis in human non-neoplastic mucosa in combination with serum bile acid quantification. Ochsenkuhn et al have reported a positive correlation between serum DCA levels and proliferation measured by flow cytometric cell cycle analysis. However, a more recent study of colorectal adenoma patients failed to detect a correlation between serum DCA and immuno-histochemical Ki-67 antigen labelling. Instead, this latter study revealed a positive correlation between serum DCA and the degree of TUNEL-positive epithelial cell apoptosis. ... 

PBNA has been tested for carcinogenicity in a number of species without conclusive results. There was no evidence of carcinogenic activity in male or female rats or in male mice fed 2500 or 5000 ppm in the diet for 2 years. The lack of carcinogenicity in rats may be related to an inability to metabolize PBNA to the known animal and human urinary bladder carcinogen P-naphthylamine. There was equivocal evidence for carcinogenicity in female mice, as indicated by the occurrence of two rare kidney tumors. Chemical-related non-neoplastic lesions, including nephropathy, karyomegaly, and hyperplasia, occurred in the kidneys of both species. 

Coumarin was tested by oral administration in two early studies in rats (Hagan etal, 1967 Bar Griepentrog, 1967 Griepentrog, 1973) and found to produce bile duct carcinomas at high levels of exposure in the latter study (lARC, 1976). However, in a re-evaluation by other pathologists of the slides from the Bar and Griepentrog (1967) study, these lesions were deemed to be non-neoplastic cholangiofibrosis and not bile duct carcinomas (Cohen, 1979 Evans et al, 1989). 

In a two-year inhalation study, male and female Fischer 344/N rats and B6C3Fi mice (six weeks of age) were exposed to 0, 94, 188 or 375 ppm [0, 235, 470 or 938 mg/m ] and 0, 188, 375 or 750 ppm [0, 470, 938 or 1875 mg/m ] nitromethane, respectively, for 6 h per day on five days per week for 103 weeks. Non-neoplastic lesions that developed with increased incidence included nasal lesions with degeneration and metaplasia of the olfactory epithelium and degeneration of the respiratory epithelium in male and female mice (National Toxicology Program, 1997). 

No treatment-related gross or histopathological lesions in the liver were observed in rats in the chronic experiment by NTP (1986), but dosed male mice had increased coagulative necrosis and hepatocytomegaly, along with increased incidences of hepatocellular adenomas and carcinomas (see Section 2.2.2.8 on carcinogenicity). Female mice, however, did not have treatment-related lesions in the liver. The highest dose (500 mg/kg/day) is indicated as a NOAEL for liver effects in rats, while the low dose (250 mg/kg/day) is indicated as a LOAEL for non-neoplastic liver lesions in... 

In a two-year study (United States National Toxicology Program, 1989 Kari et al., 1992), dose-dependent hepatic morphological changes (anisokaryosis, elevated frequency of multinucleated cells) were observed in male mice. In a long-term feeding study (0.8% in the diet) (Shibata et al., 1991), hepatic centrilobular hypertrophy was observed in males and forestomach hyperplasia in both males and females, while no non-neoplastic changes in the kidney were reported. 

Foster, C. S., Edwards, P. A. W., Dinsdale, E. A. and Neville, A. M. 1982B. Monoclonal antibodies to the human mammary gland. Distribution of determinants in non-neoplastic mammary and extra mammary tissues. Virchows Arch [Pathol Anat.] 394, 279-293. 

Non-neoplastic pigmented nevi may increase in number in patients treated with somatropin (SEDA-21, 453). 

Non-Neoplastic Advanced Lung Disease, edited by J. R. Maurer... 

No significant non-neoplastic lesions were observed in the thyroid, parathyroid, adrenal, and pituitary gland from male and female Sprague-Dawley rats maintained for 2 years on a diet that supplied 0.001, 0.01, or 0.1 g 2,3,7,8-TCDD/kg/day (Kociba et al. 1978a). Similar results were obtained in male and female Osbome-Mendel rats and in male B6C3F, mice administered up to approximately 0.071 g... 

Prenatal diagnostic X-irradiation has also been linked to increased risk of leukaemia in offspring, as has therapeutic, high-dose, ionizing radiation in childhood for other cancers and for various non-neoplastic conditions (Ron et al., 1988a Chow et al., 1996). 

Therapeutic applications These agents have a broad clinical spectrum, being used either singly or as part of a regimen in treatment of a wide variety of neoplastic diseases, for example, Burkitt s lymphoma and breast cancer. Non-neoplastic disease entities, such as nephrotic syndrome and intractable rheumatoid arthritis, are also effectively treated with cyclophosphamide. 

J2. Jones, H. E., Eaton, C., Barrow, D., Dutkowski, C., and Griffiths, K., Response of cell growth and retinoic acid receptor expression to retinoic acid in neoplastic and non-neoplastic prostate cell lines. Prostate 30, 174-182 (1997). 

No treatment-related non-neoplastic histopathological effects on hepatic tissue were found in male Sprague-Dawley rats exposed to 0, 100, or 300 ppm benzene 5 days per week, 6 hours per day for life (Snyder et al. 1978a, 1984) or in AKR/J or C57B1/6J mice similarly exposed to 300 ppm for life (Snyder et al. 1978a, 1980). 

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