Gender Differences in Susceptibility to Environmental Factors A Priority Assessment (1998) / Chapter Skim
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Appendix B: Summary of Workshop Presentations
Appendix B: Summary of Workshop Presentations
Pages 33-61
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From page 33... ...
The first panel examined the overall issue of patterns of environmental exposure among, women. The second panel focused on patterns of susceptibility to environmental factors.
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From page 34... ...
A major methodological problem in carrying out such research is that men and women do not encounter We same environmental exposures at work. For We most part, American women remain in "ghettoes of employment." Today there are more women in We workforce, but He traditional employment patterns of women have not changed significantly over He past 50 years (see Figure B1~.
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From page 35... ...
such as reproductive state, toxicological mechanisms, and individual metabolism. in general, the state-of-the-art of occupational health research is not advanced with regard to identifying, We full range of relevant variables, such as socioeconomic status and lifestyle and defining how these variables interact.
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From page 36... ...
Public administration 5% Service 24% Finance, insurance, and real estate 5% Agriculture 1% C Mining 0% Construction 1% | \Manufacturing 12% Transportation, communication, and oublic utilities 4% I Wholesale and / retail trade 21% Finance, Insurance, and real estate 9% Agriculture 4% Mining 1% L/ ' '/ I ~~\Construction 10% Wholesale and retail trade 20% Manufacturing 21% Transportation, communication, and other public utilities 10% FIGURE ~1 industrial employment of women and men by sector, 1992. Historically, Me complexities in characterizing "host factors" have led to a simple methodological solution: We wholesale exclusion of women from occupational heals studies.
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From page 37... ...
In general, far too few resources have been devoted to the systematic collection and registration of occupational exposures and health outcomes in a way that is useful and conducive to research and establishment of meaningful policy. Finally, a fundamental methodological issue confronting the panel is the "problem" statement itself: developing knowledge that will identify Slender differences in susceptibility to environmental factors.
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From page 38... ...
Environmental Exposure and Nutrition~ This topic involves many of the same paradigm issues developed in the preceding presentation: do women have different diets from men, as well as (or instead of) different environmental exposures, and does the interaction between diet arid exposure increase or decrease their risks of disease?
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From page 39... ...
More effort is needed in this area. How might researchers use the resulting data for surveillance: that is, how might women's dietary intake influence their exposures to environmental factors?
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From page 40... ...
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From page 41... ...
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From page 42... ...
Nevertheless, two of the differences between men and women that stand out in the national data are that women diet more often and consume more low-fat foods and beverages. Women's nutritional status may have its own effect on their environmental exposures.
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From page 43... ...
Many studies address environmental factors and many others consider diet, but very few consider both diet and environmental factors. Multiple Environmental Exposures Across the Lifespan The first challenge in this area is to understand what is meant by "multiple exposures." Exposure to potentially harmful substances and stresses occurs not only in environmental and occupational settings but also in residential, recreational, and even medical settings.
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From page 44... ...
However, women in the follicular stage (before ovulation) have higher plasma levels of cocaine than those in the luteal phase, when estradiol and progesterone levels are higher (Lukas, et al., 1996~.
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From page 45... ...
A classic example is We relationship between exposures to smoking and asbestos and the risk of lung cancer (see Table B-31. People with neither exposure have a rate of lung cancer of 11 in 100,000.
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From page 46... ...
In this case, gender differences may actually be protective for women. Similar evidence for Me interaction of multiple exposures over the lifespan can be seen in a recent study of Me link between smoking, and breast cancer (Ambrosone et al., 1996~.
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From page 47... ...
FIGURE ~5 Environmental tobacco smoke In the workplace. 270 TABLE B-4 Influences of Gender, Development, and Ethanol Consumption on Benzene's Effect on ET~roid Colony-Formin, Units ~7 Reduced Reduced Exposed Mice, 1 0-day Exposure Adult male Fetal male (days ~15)
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From page 48... ...
In a study of multiple exposures in the semiconductor industry, researchers followed 3,200 subjects in eight companies, equally divided between men and women and between fabrication and nonfabrication workers. Subjects were evaluated for 15 chemical agents, two physical agents, and numerous ergonomic stressors.
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From page 49... ...
The first presentation focused on a disease that affects Me human organism, while the others described laboratory studies that highlight Me kind of basic research currently under way. Epidemiology, Gender, and Environmental Influences on Multiple Sclerosis4 Multiple sclerosis (MS)
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From page 50... ...
In the United States, the highest incidence is in the northern tier of states, possibly because of the high concentration of Scandinavian immigrants in the northern states, plus some unknown environmental factor. Other known risk factors include average temperature, dairy products, meat, and sanitation.
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From page 51... ...
Like breast cancer, MS is more prevalent in high-SES women; while lifestyle factors are difficult to isolate, there does seem to be an association between MS and a diet high in dairy and meat. Estrogen Receptor Knockout Mouse Studies and Implications for Differences in Susceptibility5 Researchers at the National Institute of Environmental Health Sciences (NIEHS)
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From page 52... ...
The receptor itself is a ligand-activated transcription factor. Another very sensitive marker of response is the stimulation of lactipherin, whose gene response and mRNA increase about 300-fold in response to a single injection of hormone; but ERKO mice are totally unresponsive, again demonstrating the total lack of functional estrogen receptors.
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From page 53... ...
Preliminary data indicates that Genistein may produce ,rowth effects Trough the estrogen receptor in the uterus, but the regulation of LH negative feedback may involve a nones~o~,en receptor mechanism. Gender Differences in Metabolism and Susceptibility to Environmental Exposures6 Recent data indicate that the relatively small gender-specific differences in He metabolism of xenobiotics do not Filly explain the gender-specific adverse effects of toxicants.
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From page 54... ...
Pivotal to our general hypothesis is the observation that some currently accepted transduction pathways for toxicants evolved prior to expression of sexual reproduction. The eight-cell mouse embryo demonstrates that the AH receptor, which is a receptor for TCDD-like toxicants, exists prior to the estrogen receptor (Peters and Wiley, 19959.
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From page 55... ...
There is little hard evidence to support the concept that overlapping, pathways are the basis for the observed developmental defects, but it is often overlooked that the development of fish, reptiles, and birds are more susceptible to environmental and steroid inducers Man are mammals. Existing data make it possible to test the following specific hypothesis: sex steroid hormones and growth factor transduction pathways are shared by toxicant-induced pathways.
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From page 56... ...
share a critical transduction pathway and have opposing elects on that pathway. Evidence to support this hypothesis comes from studies of granulosa cells, in which polyaromatic hydrocarbons TCDD in this case-decrease the cell's ability to produce estradiol and also reduce estrogen receptor levels, thus demonstratin, two different "hormone disruptin;," mechanisms.
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From page 57... ...
FIGURE ~8 Estrogen protective effects against TCDD. 57 this is that levels of toxicants Mat produce major developmental changes in lower vertebrates have less effect on the reproductive development of rats.
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From page 58... ...
These same concepts can be extrapolated from developmental defects to interactions between and among steroid hormones, growth factors, and toxicants and to changes in the proliferative potential of certain cell types and Me induction of precancerous states. Cells may be likely to be more (or differentially)
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From page 59... ...
Assays developed in cell or animal studies have now been applied to humans to provide markers of early biological effects that will lead to cancer. Researchers are also focusing on He role of oncogenes and tumor suppressor genes as markers of susceptibility.
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From page 60... ...
Estimates of individual exposure had to be reconstructed from historical or imputed data and all possible risk factors for breast cancer could not be accounted for. Therefore, these studies need to be followed up by prospective epidemiology studies as well as laboratory investigations of the associations.
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From page 61... ...
vigorous application of animal models to study underlying regulation of environmental carcinogenesis; and 5. identification of biological causality between genetic susceptibility markers and gender-related human cancers.
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