National Cancer Institute, NCI

The National Cancer Institute (NCI) database is a collection of more than half a million structures, assembled by NCI s Developmental Therapeutics Program (DTP) or its predecessors in the course of NCTs anti-cancer screening efforts that started in the late 1950s (plus the more recent anti-HIV screening) [37-39]. Approximately half of this database is publicly available without any usage restrictions, and is therefore called the "Open NCI Database. For each of these structures (more than 250 000) the DTP record contains at least the chemical structure as a coimection table and an NCI accession number, the NSC number. 

Based on tests with laboratory animals, aniline may cause cancer. The National Cancer Institute (NCI) and the Chemical Industry Institute of Toxicology (CUT) conducted lifetime rodent feeding studies, and both studies found tumors of the spleen at high dosage (100 —300 mg/kg pet day of aniline chloride). CUT found no tumors at the 10—30 mg/kg per day feeding rates. The latter value is equivalent to a human 8-h inhalation level of 17—50 ppm aniline vapor. In a short term (10-d) inhalation toxicity test by Du Pont, a no-effect level of 17 ppm aniline vapor was found for rats. At high levels (47—87 ppm), there were blood-related effects which were largely reversible within a 13-d recovery period (70). 

A scientifically evaluated and fully referenced data bank, developed and maintained by the National Cancer Institute (NCI). It contains some 8,000 chemical records with carcinogenicity, mutagenicity, tumor promotion, and tumor inhibition test results. Data are derived from studies cited in primaiy journals, current awareness tools, NCI reports, and other special sources. Test results have been reviewed by experts in carcinogenesis and mutagenesis. 

Camptothecin was discovered as an active anticancer drug isolated from the bark of Camptotheca acuminata. The anticancer activity of camptothecin was discovered in the 1960s by the National Cancer Institute (NCI) as part of a systematic effort to screen for novel anticancer agents derived from natural products. Monroe Wall and Mansuhk Wani identified the chemical structure of camptothecin. They also identified the chemical structure of taxol, again under the auspices of the NCI. Susan Hoiwitz was contracted by the NCI to elucidate the anticancer mechanisms of camptothecin. She found in the early 1970s that camptothecin induced DNA breaks and attested DNA and RNA synthesis. However, it is approximately 12 years later, only after DNA topo-isomerase I (Topi) had been identified in human cells, that Leroy Liu and his coworkers found that Topi was the cellular target of camptothecin [reviewed in [1]. 

Increased mortality was observed in both male rats (at doses of 20.4 mg/kg/day and above) and male mice (at doses of 0.46 mg/kg/day and above) in a 2-year bioassay conducted by the National Cancer Institute (NCI 1978). The authors attributed the excessive mortality in the male rats to treatment-related toxic nephropathy. The high mortality in male mice was possibly due to fighting since no other treatment-related cause for the deaths could be determined. Survival in females of both species was unaffected by endosulfan (NCI 1978). However, survival was significantly decreased in female rats that consumed 5 mg/kg/day for 2 years (FMC 1959b), and in female mice that consumed approximately 2.9 mg technical endosulfan/kg/day for 2 years (Hack et al. 1995 Hoechst 1988b). In these studies, survival in male rats was not affected at 5 mg/kg/day for 2 years (FMC 1959b) and survival in male mice was not affected at 2.51 mg/kg/day for 2 years (Hoechst 1988b). 

NCI. 1968. Evaluation of carcinogenic, teratogenic and mutagenic activities of selected pesticides and industrial chemicals. Volume I Carcinogenic study. Prepared by Bionetics Research Labs, Inc., Bethesda, MD National Cancer Institute. NCI-DCCP-CG-1973-1-1. 

NCI (1996) Clinical Development Plan Genistein. National Cancer Institute (NCI) Chemoprevention Branch and Agent Development Committee. J Cell Biochem. 26S 114-26. 

A number of calculators are available on the Internet to estimate a patient s risk of developing breast cancer. The National Cancer Institute (NCI) has an online version of the Breast Cancer Risk Assessment Tool that is considered to be the most authoritative and accurate standard (www.cancer.gov/ bcrisk-tool). The Breast Cancer Risk Assessment Tool was designed for health professionals to project a women s individualized risk for invasive breast cancer over a 5-year period and over her lifetime. 

The National Cancer Institute (NCI) research resources database lists scientific information, tools, reagents, and services for cancer researchers on its website at http //resresources.nci.nih.gov. 

A review of data from 250 chemicals found an 82% concordance between results of carcinogenicity testing in the mouse and the rat (Purchase, 1980). Haseman et al. (1984a) reported a concordance of 73% for 60 compounds studies in both species. However, 30 to 40% of 186 National Cancer Institute (NCI) chemicals were found to be positive in one species and negative in the other (Gold et al., 1984). It is reasonable to conclude that neither rodent species will always predict the results in the other rodent species or in humans, and that the use of two species will continue until we have a much better understanding of the mechanisms of carcinogenesis. 

NCI National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government s principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http //cancer.gov. [NIH]... 

In a study reported by the National Cancer Institute (NCI 1980), rats exposed to 16-1,694 mg/kg/day (100-10,000 mg/L) and mice exposed to 25-2,642 mg/kg/day (100-10,000 mg/L) phenol in drinking water exhibited no indication of histopathological effects on the respiratory system after 13 weeks of exposure. No histological abnormalities of the respiratory tract were observed in rats or mice exposed to 2,500 or 5,000 ppm phenol in drinking water for 103 weeks (mg/kg/day doses 322 or 645 for male rats 360 or 721 for female rats 590 or 1,180 for male mice 602 or 1,204 for female mice) (NCI 1980). 

The carcinogenicity of orally administered phenol was examined in rats and mice in a study reported by the National Cancer Institute (NCI 1980). Rats and mice received 0, 2,500, or 5,000 ppm in drinking water for 103 weeks. Calculated intakes for rats were 322 and 645 mg/kg/day for males and 360 and 721 mg/kg/day for females. Calculated intakes for mice were 590 and 1,180 mg/kg/day for males and 602 and 1,204 mg/kg/day for females. Statistically significant increased incidences of pheochromocytomas of the adrenal gland and leukemia or lymphomas were observed in male rats exposed to 322 mg/kg/day (2,500 ppm), but not in male rats exposed to 645 mg/kg/day (5,000 ppm). No significant effects were seen in female rats or mice of either sex exposed to either exposure level. Since cancer occurred only in males of one of the two species tested and a positive dose-response relationship could not be established, these results are inconclusive regarding the carcinogenic potential of orally administered phenol. 

Nonneoplastic proliferative lesions of the forestomach were observed in high-dose Osborne-Mendel rats in the chronic gavage study of 1,2-dibromoethane conducted by the National Cancer Institute (NCI 1978). These consisted of acanthosis and hyperkeratosis of forestomach squamous epithelium. Similar lesions occurred in high-dose B6C3Fi mice. These dose levels are not plotted and recorded in Figure 2-2 and Table 2-2, respectively, since these doses also caused forestomach squamous cell tumors. 

There are data from animal studies in mice, rats, and pigs that indicate that both carbohydrate metabolism and lipid metabolism may be affected by exposure to heptachlor or heptachlor epoxide (Enan et al. 1982 Halacka et al. 1974 Kacew and Singhal 1973 Pelikan 1971). Alterations in gluconeogenic enzymes and an increase in cellular steatosis in the liver have been reported. Granulomas and fibrotic liver have also been observed. In addition, hepatocellular carcinoma was identified as causally related to heptachlor in the diet in a mouse study conducted by the National Cancer Institute (NCI 1977). The existing evidence suggests that heptachlor and heptachlor epoxide are hepatic toxicants. 

Caspase inhibitors Antioxidating enzyme enhancers National Cancer Institute (NCI)... 

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