Spontaneous tumors

It is not appropriate to generali2e the carcinogenicity of this class of compounds. Nitrofura2one appears to increase the incidence of benign mammary tumors in rats. The tumorigenic activity of fura2ohdone is expressed by an increase in the incidence of spontaneous tumors in both mice and rats. Bioassays of nitrofurantoin in several species of mice and rats failed to reveal any evidence of direct tumorigenic activity. Ovarian tumors have been reported in B C F mice, but these are beheved due to an indirect expression of toxicity (14,15). 

In assessing animal data, careful attention must be paid to the quality of the data, the incidence of spontaneous tumors in the control population, consistency if more than one study is available, and statistical validity. If the exposure route and experimental regimen employed do not agree with the most likely mode(s) of human exposure (e.g., intramuscular injection), the data must be interpreted cautiously. Consideration should be given to data on metabolism of the compound by the animal species tested, as compared with metabolism in humans if this information is known. If only in vitro data are available, only qualitative estimates may be possible because of uncertainties regarding the association between in vitro results and human or animal effects. The availability of associated pharmacokinetic data, however, may allow development of a rough quantitative estimate. 

The choice of species and strain to be used in a carcinogenicity study is based on various criteria including susceptibility to tumor induction, incidence of spontaneous tumors, survival, existence of an adequate historical data base, and availability. 

Given that, at least under some conditions, assays using these models tend to blow up (have high spontaneous tumor rates) once the animals are more than eight or nine months of age, how critical are age and other not currently apprehended factors to optimizing both sensitivity and specificity ... 

Sher, S.P., Jensen, R.D. and Bokelman, D.L. (1982). Spontaneous tumors in control F344 and Charles River CD rats and Charles River CD-I and B6C3F1 mice. Toxicol. Lett. 11 103-110. 

Effects of three commercially produced calcium silicate insulation materials were examined in rats by inhalation and intraperitoneal injection. Exposure to lOmg/m of respirable dust for 7 bours/day, 5 days/week for 12 months bad no effect on tbe survival of treated animals compared with controls. Although two pulmonary neoplasms, one malignant and one benign, were found in exposed animals, neither was the cause of death, and the incidence was not significantly different from the control group, where no mmors were found. One peritoneal mesothelioma was found in an animal from one of the inhalation groups, but tbis was considered to be a spontaneous tumor as none of over 100 animals injected intraperitoneally with 25 mg of calcium silicate developed these tumors. 

Kanisawa M, Schroeder HA Life term studies on the effect of trace elements on spontaneous tumors in mice and rats. Cancer Res 29 892-895, 1969... 

Some drugs situations are frankly confusing and need to be explored in greater depth. For example, tumor necrosis factor (TNF) is produced in the body as a natural defense against the many spontaneous tumors that arise in the body and has been suggested as a treatment for cancer, which may very well be effective under some conditions. However, TNF is also believed to be involved in the pain associated with rheumatoid arthritis, and monoclonal antibodies with specific activity against TNF are now on the market. The use of TNF is therefore a complex issue and needs to be evaluated with considerable care. 

We examined the antitumor effect of CVS against spontaneous tumor metastasis after surgically removing a s.c.-inoculated primary Meth A tumor mass from the right foot pad in BALB/c mice, Fig. (6)-Protocol A. The survival rates of the Meth A tumor-inoculated mice markedly increased when CVS was injected i.t. three times every other day following the tumor inoculation, Fig. (7)-A. A similar result was obtained in the EL-4 lymphoma and C57BL/6 syngeneic system (data not shown). 

Lymphocytic Tumors of Thymic Origin. The appearance of spontaneous tumors (e. . SAKRTLS-13) in AKR and C58 mice (27) is quite common. Other thymic tumors can also be induced chemically (28) (BALENTL—3, -5 or P-1798 Table I) or virally (Moloney leukemia virus (29)). in the early stage of tumor development they are confined to the thymus, but later the tumor is metastasized to the spleen, liver, kidney, and lymph nodes. 

There is an increased blood flow in brain tumors (ref. 589), and the blood-brain barrier is leaky in and around 9L tumors because the blood vessels associated with these (ref. 568), and other (ref. 565-567), tumors are fenestrated. This well-known leakiness of tumor capillaries, which in the case of brain tumors includes breaches in the blood-brain barrier (ref. 566,568 cf. Section 12.2), would allow extravasation of small particulate matter (cf. ref. 590-594) or LCM. Once in the tumor area, LCM remain there because of an affinity for tumor cell surface components (cf. ref. 531 see also Chapter 14). At least 4 different types of experimental tumors in rats (C6 glioma, 9L gliosarcoma, Novikoff hepatoma, and Walker-256 carcinosarcoma), as well as several spontaneous tumors in dogs (ref. 570), do interact with LCM in a preferential manner (cf. Chapters 12 and 13), suggesting that LCM affinity may be for tumor cells in general (ref. 531). 

The SD rat is a commonly used laboratory animal. However, it has limitations when used to evaluate the effects of chemicals on the endocrine system, including the pituitary and mammary gland, because of a high spontaneous tumor incidence in these organs. At about 9-12 months of age, the SD rat begins to experience prolonged periods... 

Administration of separate isomeric forms of BHC (a, 6) produced liver tumors and lung metastases in mice, whether bred for a low or high incidence of spontaneous tumors (ref. 100). Effects of BHC reported on exposed humans Include liver cirrhosis and chronic hepatitis in 8 workers also cases of aplastic anemia and leukemia (ref. 100, p. 157). Animal studies to date focused primarily on the reproductive effects of lindane are both insufficient and inconclusive. Earl et al. reported fetotoxic effects (stillbirths, perinatal deaths) in beagles (ref. 

Studies on mammary tumors have shown that the effect of dietary fat can be demonstrated with spontaneous tumors and with tumors induced by a variety of chemical or physical agents (D5). Furthermore, experiments in our laboratory have shown that dietary fat effectively increases the yield of mammary tumors induced in rats by DMBA, even when the high-fat diet is first instituted one to two weeks after treatment with a carcinogen ( 7 ). These observations suggest that dietary fat is not involved in tumor initiation but acts by providing a more favorable environment for proliferation of tumor cells. 

Hbb,h3,+ mice Murine tumor xenografts Spontaneous tumors in companion animals... 

A total of 31 of the 32 studies planned for the 21 compounds chosen for evaluation were completed. The results were reported by Storer et al. (2001). The overall spontaneous tumor incidence was low, 2.8 % for males and 6 % for females in studies without transponders (microchips for animal identification) and 8 % for males and 11.3 % for females in studies... 

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