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5. Laboratory Methods
Pages 19-24

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From page 19...
... However, it also emphasized that there are major drawbacks in the standard procedure for determining carcinogenicity of compounds, i.e., the bioassay in animals fed the test substance for a major portion of their lifetime. These longterm bioassays lack sensitivity, they may produce false negative results, and, because of the high doses given to animals, extrapolation of the results to determine the response of humans exposed to lower doses cannot be accomplished with any degree of certainty (National Research Council, 1982~.
From page 20...
... Finally, there are no reliable methods for the extrapolation of data from animal studies to determine the response in humans. Since current procedures are probably of little or no value for assessing the risk of nutrient-induced tumor modification, it is likely that an entirely new approach will be required (National Research Council, 1982, Chapter 18~.
From page 21...
... Further studies are needed to unravel the specific mechanisms of this early stage of carcinogenesis and to identify dietary constituents that act at that time. Studies in laboratory animals have indicated that food contains many inhibitors of carcinogenesis (National Research Council, 1982, Chapter 15~.
From page 22...
... Accordingly, attention should be directed toward finding ways to evaluate specific dietary components for their early neoplastic or inhibitory effects in humans and to identify early markers that can be used to predict the likelihood that clinical cancer will develop in humans. For example, the early stages of neoplasia can be detected by the presence of hepatic foci with altered enzymatic activity (Pitot _ al., 1980; Potter, 1981)
From page 23...
... Because these blocking agent s may affect carcinogenrnetabolizing systems that are tissue enzymes, it will be necessary to select readily available as well as suitable tissues in humans. An alternative strategy i s to admini ster noncarcinogenic prototype compounds that are metabolized in a fashion similar to that of known carcinogens and then to assess their metabolism by measuring blood and urine samples or, possibly, by quantitating volatile metabolites that are exhaled.
From page 24...
... In addition, attempts should be made to refine cytogenetic procedures. · Short-term technique s should be devised to detect the early effects and to quantify the impact of compounds suspected of acting as promoters or cocarcinogens in humans.


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