Carcinogens positive control

Untreated BALB/c 3T3 cells and solvent-treated cells were used as negative controls. Positive controls were represented by cells treated with the well-known carcinogen 3-MCA (2.5 pg/mL). After 48 h, cells were replenished with fresh normal culture medium and maintained in culture for 4-6 weeks, with biweekly medium changes. Cells were then fixed with methanol, stained with 10% aqueous Giemsa, and scored for foci formation. In order to calculate the number of cells... 

Metofluthrin (I) The committee determined that the new data were sufficient to support a mitogenic mode of action for the development of liver tumors in rats exposed to metofluthrin in the carcinogenicity study. The report summarized mode of action study data that characterized effects such as increased P450 enzyme levels, increased smooth endoplasmic reticulum, hepatocellular hypertrophy, hepatocellular proliferation, and inhibition of intracellular communication, which were described as steps leading to tumor development via a nongenotoxic mechanism (i.e., mitogenicity). Some of these studies used sodium phenobarbital as a positive control,... 

Mauthe et al. (2001) reported the experimental procedures used in the tests, performed in agreement with the indications given by the ACT (Alternative Carcinogenicity Testing) Committee. In all experiments, benzo[a]pyrene was used as a positive control. 

In research, benzo(a)pyrene (BP) is used extensively as a positive control in a variety of laboratory mutagenicity and carcinogenicity short-term tests. It is not produced commercially in the United States. 

Benzo[a]pyrene. Benzo[a]pyrene is a potent experimental skin carcinogen, and it is often used as a positive control in bioassays of other agents. Mixtures of PAHs that include benzo[a]pyrene such as coal tar were shown to be dermal carcinogens in animals as early as 1918 (Yamagiwa and Ichikawa 1918). In its role as a positive control, benzo[a]pyrene is usually administered at a single dose level, and thus quantitative evaluation of dose-response relationships is not possible. 

Because the genotoxic activity of benzo[a]pyrene is well established, it is frequently used as a positive control to demonstrate the sensitivity of various test systems to detect the genotoxic action of unknown compounds. It also serves as the model compound for PAHs, and the available information on the formation of metabolites and structure of benzo[a]pyrene can theoretically be used to predict potential genotoxicity/carcinogenicity of other PAHs that have not been as extensively studied. 

Table 6 contains the mean value of three separate experiments. A comparison of the intestinal and peritoneal cell counts reveals that the ampicillin treatment reduced the intestinal cell counts approximately a hundred-fold without affecting the Salmonella titer. Cycasin alone (positive control) resulted in the anticipated rise in MF for typhimurium ampicillin alone did not alter the spontaneous MF, and mice treated with both ampicillin and cycasin were approximately the same as the negative control. The reduction of intestinal microorganisms by ampicillin and the resultant inability to detect mutagenic activity after administration of cycasin parallel the finding in carcinogenic studies. In germ-free animals no tumors were found after administration of cycasin (Spatz et aL, 1967). 

Tubal ligation is another procedure that has shown potential for risk reduction. However, it is not recommended as a sole procedure in prophylaxis. Protective effect may be due to limiting exposure of the ovary to environmental carcinogens. A case-control study conducted by Narod and colleagues found that a history of tubal ligation in /f RCA-positive women was associated with a statistically significant 63% reduction in risk.22... 

A method proposed by Schweder and Spjotvoll (1982) is based on a plot of the cumulative distribution of observed p values. Farrar and Crump (1988) have published a statistical procedure designed not only to control the probability of false positive findings, but also to combine the probabilities of a carcinogenic effect across tumor sites, sexes, and species. 

Another approach to controlling the false positive rate in carcinogenicity studies was proposed by Haseman (1983). Under this rule, a compound would be declared a carcinogen if it produced an increase significant at the 1% level in a common tumor or an increase significant at the 5% level in a rear tumor. A rare neoplasm was defined as a neoplasm that occurred with a frequency of less than 1% in control animals. The overall false positive rate associated with this decision rule was found to be not more that 7-8%, based on control tumor incidences from NTP studies in rats and mice. This false positive rate compares favorably with the expected rate of 5%, which is the probability at which one would erroneously... 

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