Bioassays, carcinogens active

Several short-term bioassay procedures (3-14) have been developed recently which are applicable to detecting mutagenic and potential carcinogenic activity of organic substances. The SaimoneJla/mammalian mlcrosome assay or Ames Test (13-13] has been the most frequently applied and its efficacy has been well documented. This assay has also been applied to complex mixtures (19-22) to reduce greatly the time... 

All PCB mixmres adequately tested in mice and rats have shown carcinogenic activity. For example, of 20 rats fed Aroclor 1242 at 100 ppm in the diet for 24 months, 11 developed liver tumors, of which 3 were hepatomas. A significant incidence of hepatocellular neoplasms was found in female rats but not males in another smdy of Arochlor 1242 in the diet. Evidence from bioassays suggests that the less highly chlorinated PCBs (e.g., Aroclor 1242) have less carcinogenic potential than the more highly chlorinated mixtures (e.g., Aroclor 1254). ... 

In no instance did the synthetic retinoid possess as great an inhibitory capacity as do retinol or retinyl acetate. In addition, the provitamin g-carotene had no effect on mutagenicity of 2-fluorenamine in Salmonella regardless of the carcinogen activation system (Tables III and IV). Thus, 3-carotene would apparently require enzymatic cleavage to vitamin A in order to have an effect in this ijri vitro bioassay and exerts no role by itself in modulating the metabolism of chemical carcinogens in the model system. 

In 2 year carcinogenicity inhalation bioassays in rats and mice, there were no indications of carcinogenicity in male rats, while equivocal evidence was found in female rats. These findings were evidenced by increased fibroadenomas of the mammary gland. In these 2 year studies in mice, there was no evidence of carcinogenic activity in males and females. 

These SAR considerations have been captured in EPA s OncoLogic Cancer Expert System for predicting carcinogenic potential of chemicals completed in 1999-2000 (Woo and Lai 2005 Woo et al. 1995). In 2006, the NTP completed the cancer bioassay of a number of new congeners of polychlorinated dibenzofurans and PCBs. The results of these studies are summarized in the table below and compared to the OncoLogic predictions. As can be seen from the table, the mechanism-based SAR approach of the OncoLogic system allowed the system to accurately predict the carcinogenic activities. 

The corroborative evidence of the carcinogenic activity of tobacco smoke provided by animal bioassays and in vitro studies and the chemical similarity between mainstream smoke and ETS clearly establish the plausibility that ETS is... a human lung carcinogen. 

The development of short-term genetic bioassays has provided relatively simple, sensitive, and rapid bioassays for mutagenic and potential carcinogenic activity. Short-term genetic bioassays have been particularly useful in evaluating combustion emissions This paper summarizes the results of studies where short-term genetic bioassays have been used in the following areas ... 

The mutagenic and carcinogenic activities of the extractable organics from a series of diesel and gasoline particle emissions have been compared in a battery of short-term bioassays (14). 

Chemicals commonly are screened for carcinogenic potential using two basic types of tests, animal bioassay and in vitro assays. Animal bioassays for carcinogenic activity are most commonly conducted in mammalian species, such as rats, mice, and hamsters. The second type of assay using in vitro procedures screens either for transformation in mammalian cells or for the mutagenic potential of a chemical in a bacterial system after metabolic activation of the test substance (130). Other test systems, such as dominant-lethal mutation tests, translocation tests that screen for chromosomal ab-... 

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). 

Cycloheximide is genotoxic in Escherichia coli with metabolic activation and in the mouse sperm morphology assay. Carcinogenicity bioassays in the mouse and rat are inconclusive. ... 

TOPAMAX, a sulfamate-substituted monosaccharide approved for use as an antiepileptic drug at oral doses of up to 400 mg per day, exhibits carbonic anhydrase inhibition activity [15]. A 21-month dietary study in mice with TOPAMAX resulted in increased incidence of bladder tumors similar to those observed in the mouse carcinogenicity bioassay with brinzolamide at two years. 

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