Carcinogens and Anticarcinogens in the Human Diet A Comparison of Naturally Occurring and Synthetic Substances (1996) / Chapter Skim
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6 Conclusions, Recommendations, and Future Directions
6 Conclusions, Recommendations, and Future Directions
Pages 335-358
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From page 335... ...
The committee was also asked to develop a strategy for selecting adclitional natural substances for toxicological testing. This subject is immense because by far the major source of expo sure to naturally occurring chemicals is the diet, and the concern that dietary factors might play a major role in human cancer cause lion.
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From page 336... ...
that the great majority of indiviclual naturally occurring ant! synthetic chemicals in the cliet are present at levels below a significant biologic effect, so low that they are unlikely to pose an appreciable cancer risk and 2)
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From page 337... ...
It is not clear the clegree to which, in aggregate, naturally occurring and synthetic chemicals present an appreciable risk. It is apparent that existing concentration and exposure data and current cancer risk assessment methods are in sufficient to definitively address the aggregate roles of naturally occurring or synthetic dietary chemicals in human cancer causation and prevention.
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From page 338... ...
Current regulatory practices leave applied far greater stringency to the regulation of synthetic chemicals in the diet than to naturally occurring chemicals. The committee reviewed MARC, NTP, and other data to ascertain the status of carcinogenicity testing of natu rally occurring versus synthetic chemicals.
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some other fungal toxins. The human diet also contains anticarcinogens that can reduce cancer risk.
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From page 340... ...
Based in part on this limited sample, the committee conclucled that there is no clear difference between the potency of naturally occurring and synthetic carcino yens that may be present in the human diet. In general, both types of chemicals have similar mechanisms of action, similar positivity rates in roclent bioassay tests for carcinogenicity, and encompass similar ranges of carcinogenic potencies.
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From page 341... ...
In its assessment of traditional epidemiologic approaches to identifying dietary carcinogens and anticarcinogens, the committee concluded that these can be beneficially expanded by incorporating into research designs biochemical, immunologic, and molecular assays that utilize human tissues and biologic fluids. Furthermore, incorporating the identification of biologic markers into these ap preaches may provide early indicators of human carcinogenicitylong before the development of tumors.
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From page 342... ...
for expanclect epidemiologic studies, more human exposure ciata, improved and enhanced testing methods, more detailec! data on dietary components, and further mechanistic studies, if these gaps are to be filled.
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From page 343... ...
uncertainties, especially in providing quantitative estimates of dietary cancer risk to humans or the magnitude of protection by anticarcinogens. These uncertainties relate to the variability of the composition and caloric content of the human diet and the bioas say's inability to mimic this range of variability.
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From page 344... ...
Selectec] acictitional substances should be subjected to appropriate testing in order to develop a more comprehensive database on which to base compari sons of the potential cancer risks or protective effects of naturally occurring ant!
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Since most of the present short term tests detect DNA reactive compounds, new methods are neeclec! for screening chemicals for nongenotoxic endpoints such as cell proliferation, hormonal effects, receptor mectiated events, ant!
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From page 346... ...
Further studies are needed to elucidate the precise mechanisms and to better define what is optimal or excess caloric intake. Dietary fat has also been associated with increased risk of some forms of can cer, but it is not clear if this is related to the high caloric contribu lion of fat, to specific constituents in foods high in saturated fats (such as specific fatty acids or other lipid oxidation proclucts)
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From page 347... ...
Resources The conclusions and recommendations of this report indicate that a better understanding is neecled of the role of specific dietary naturally occurring and synthetic chemicals in cancer causation and prevention. This is an extremely complex task.
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From page 348... ...
Also being iden tided are alterations in pathways of signal transduction, the cascade of cytoplasmic events involving numerous protein kineses that eventually trigger alterations in gene expression in the nucleus by
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From page 349... ...
Epidemiology The advantages and limitations of various types of epidemiologic studies, including ecologic, case control, cohort, intervention, and molecular epidemiology studies are discussed in Chapter 4. Since results from these studies have suggested that a major fraction of human cancer is due to dietary factors, it is appropriate to extend this approach to identify with greater certainty the specific factors and types of cancer involves!
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From page 350... ...
that wtIt improve the accuracy of these assessments or correct for errors when they are non differential (e.g., Rosner and Willett 1988~. To further explore the hypothesis that excessive caloric intake per se may be a major risk factor for human cancer, biologic markers that assess specific effects of excess or limiter!
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From page 351... ...
Rodent and In Vitro Assays Rodent bioassays, short term tests in rodents, and in vitro assays, including recently developed cellular and molecular biology meth oafs, are summarized in Chapter 4. The committee agreed that although many of these assays provide useful information, it is important to stress that they serve only as screening tests (NRC 1993b)
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From page 352... ...
A recent approach, inter esting although fraught with difficulties, is to feed rodents a homog enate of an actual daily human Western type cliet, to assess the total effects of the human cliet on cancer induction, when testing alone or in combination with specific natural or synthetic chemicals (Rozen et al.
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From page 353... ...
As clescribed in previous chapters of this report, several components of the diet have been identified that can increase or decrease the risk of developing cancer in experimen tat animal or in vitro assays. Determining with greater certainty which of these components are significant contributors to cancer risk in humans is necessary so that an optimum diet can be recom menclecI to the American public (NRC 19821.
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From page 354... ...
As we identify those naturally occurring constituents that either enhance or inhibit human cancer, and define the conditions and concentrations that govern their actions, we can expect processing to play a large role in increasing the protective potential of diet, as it has previously played a role in improving nutritional quality. Over many centuries plants, and to a lesser degree animals, have been optimized as human food sources by selection and breecling for such desirable characteristics as safety, size, color, flavor, yield, and resistance to disease.
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From page 355... ...
should facilitate further improvements in the qual ity of the food supply with respect to cancer prevention. Specifi cally, as naturally occurring dietary chemicals that either enhance or inhibit human cancer risk are identified, these chemicals will be cancliciates for appropriate modification through food biotechnol ogy.
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From page 356... ...
Finally, as specific naturally occurring dietary chemicals are iden tiffed that either enhance or inhibit cancer risks in humans, it will be possible to better formulate specific dietary guidelines for the American public. It may also be possible to utilize this informa tion to mock*
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From page 357... ...
Pp. 83~110 in Cancer Prevention and Control, P
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