Carin Smit's response to Dr. Plumb's article. If only those who physically worked in the WTC site during and after the blasts showed a higher cancer incidence (statistically significant) vs. people living in the proximity, (the latter didn’t develop cancers in the wake of the jetliner crashes), I would like to suggest that this population needs to be examined for nitrosamines or nitrosopyrrolidines. There appears to be a very high correlation between inhaling smoke, and compounds related to burnt organic matter and the immanent development of cancers. I have reviewed just the lab results of just over 200 patients who have been tested for DNA Adducts, Lymphocyte sensitivity for toxic elements (chemicals and metals) whom I’ve seen in my practice and have had opportunity to review in other practices, and have found that high nitrosamine and nitrosopyrrolidine levels appear to be ;inked to carcinogenic risks due to epigenetic impacts via DNA Adducts. http://www.tcmda.com/Global/Aminrapporter/MIT%20nitrosamines%20report%20final.pdf Environmental Guidelines and Regulations for Nitrosamines: A Policy Summary Prepared for CO2 Technology Centre Mongstad by: Dr. Noelle E. Selin Assistant Professor of Engineering Systems and Atmospheric Chemistry Engineering Systems Division and Department of Earth, Atmospheric and Planetary Sciences Massachusetts Institute of Technology 77 Massachusetts Avenue (E40-379) Cambridge, MA 02139-4307 USA +1-617-324-2592 selin@mit.edu http://mit.edu/selin/ Page Two FINAL REPORT Here is an excerpt from the above report: Figure 1. Structure of nitrosamines. From Luan et al., 2005. Page Three Figure 2. Structure of N-nitrosodimethylamine (NDMA). From California Environmental Protection Agency, 2006. 2. Health Risks of Nitrosamines The health risk of most concern for environmental levels of nitrosamine is carcinogenicity. Exposure to nitrosamine has been shown to form tumors in laboratory animals, and have been linked in epidemiological studies to human cancers including pancreatic cancer (Risch, 2003) and childhood brain tumors (Huncharek and Kupelnick, 2004). Nitrosamines are classified by a number of international organizations and regulatory authorities as to their carcinogenicity. Under the International Agency for Research on Cancer (IARC), which is part of the World Health Organization (WHO), NDMA and NDEA are classified as Group 2A substances (probably carcinogenic to humans). The European Union categorizes NDMA and NDEA as category 1B (Presumed to have carcinogenic potential for humans; largely based on animal evidence). In the US, the Environmental Protection Agency classifies both NDMA and NDEA as a “probable human carcinogen (category B2)” under its 1986 carcinogen assessment guidelines. 5. Environmental Levels: A Survey High concentrations of NDMA have been measured in ground water near rocket engine testing facilities, as mentioned above (Mitch et al., 2003). Clinical Practice – Comment: I lost two patients in my practice this year, both with very high nitrosamine and nitrosopyrrolidine levels. Both had been smokers and inhaled significant amounts of burnt organic material across a lifetime. The one patient had metastatic liver cancer and the other metastatic melanoma. Here’s another excerpt from a significant Peer Review Journal: Cardnogenesis Vol.5 no.ll pp.1381 -1393, 1984 Commentary Relevance of nitrosamines to human cancer Helmut Bartsch and Ruggero Montesano Division of Environmental Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert-Thomas, 69372 Lyon Cedex 08, France Page Four Introduction It is now about three decades since the hepatocarcinogenic effect of N-nitrosodimethylamine (NDMA)* was demonstrated in rats (1) and the suggestion was made that N-nitrosamines can be formed following nitrosation of various amines (2). Direct proof that such nitrosation reactions can occur was provided by Ender et al. (3) who identified NDMA in nitrite preserved fish-meal, and by Sander and Seif (4) who demonstrated the formation in vivo of a nitrosamine in the acidic conditions of the human stomach. Since then, because of the potent carcinogenicity, wide environmental occurrence and easy formation of nitrosamines, considerable efforts have gone into determining their levels in the external and internal human environment, and attempts have been made to assess exposure and to correlate it with human cancer at specific sites. Fundamental research into molecular and cellular mechanisms of carcinogenesis has also concentrated on N-nitroso compounds (NOC), to find out why and how this class of carcinogens produces tumours in up to 40 animal species (5,6) and displays remarkable species, organ and cell specificity (7—11) and a wide variety of genetic effects (12,13). Human exposure to NOC The introduction of the chemi-luminescence detector (Thermal Energy Analyzer) by Fine et al. (14) represented a breakthrough in nitrosamine analysis and made it possible to assess human exposure to (mostly) volatile nitrosamines. Today, reliable methods for the analysis of a wide range of nonvolatile NOC are still not available, although progress has been made (15-18). The occurrence of NOC in several matrices and the resulting potential human exposure have been tabulated (10,19,20 and Tables I-III). Such can be divided into endogenous exposure, though formation of NOC in vivo from precursor amines and nitrosating agents (Table I), and intake of preformed NOC from occupational and environmental sources (Tables II and III). Because of recent developments in detection methods, in the following we give some emphasis to endogenously formed NOC. This shall, however, not detract from the fact that human exposure to performed NOC from a variety of sources is firmly established. Occupational sources of exposure are: 1. Leather tanneries 2. Rubber and tyre industries 3. Metal working industries 4. Chemical industries 5. Rocket fuel 6. Dye manufacture 7. Surfactant production 8. Foundries 9. Fish processing Page Five Metabolism and formation of DNA adducts Nitrosamines produce various adverse biological effects, including induction of tumours following metabolic conversion into reactive intermediates which react with various cellular macromolecules; this process is considered as one critical determinant in the carcinogenicity of nitrosamines. The various forms of microsomal enzymes responsible for this metabolic activation and the nature of the metabolites formed have been described (58 — 60). Various organs and cells from different species, including human beings, have been shown to be capable of carrying out such metabolic transformation, as determined by the detection of various metabolic products (e.g., carbon dioxide, aldehydes) and/or initial DNA alkylation (e.g., 7methylguanine). One of the gene areas impacted on DNA by Nitrosamines or Nitrosopyrrolidines appears to be on the DNA Lygase or DNA Repair gene. Another place where significant mischief is seemingly done is: the SOD1 gene, which protects against super-oxides inside cells and therefore against intra-cellular damage by chemical and metal compounds which are toxic…. Here is a typical example of a smoker’s Lymphocyte Sensitivity test: note the nitrosamine levels. Page Six The following patient lives in the flight path of jet-liners near an international airport in South Africa, which poses the question what role jet-fuels play in nitrosamine and nitrosopyrrolidine deposition and whether that might not have been the critical cause for the higher incidence of cancer for those who worked at WTC site….? This patient is 34 years of age and was diagnosed with stage III testicular cancer 2 years ago and has never once smoked in his life: This same patient’s DNA Adducts are telling: Page Seven The following is the DNA Adduct test of the first of two deceased patients (a smoker who stopped smoking 20 years ago): His Lymphocyte sensitivity test shows the dramatic issues with both Nitrosamines and nitrosopyrrolidines: Page Eight Please note the amount of Cell-Free DNA recorded for this patient – this test was done 6 weeks before his death: Here is the DNA Adducts test result of a male patient (ex smoker) with significant oxidative stress and neurological and mood problems: again note the nitrosopyrrolidine levels – he owns a carpeting company and industrial warehousing facility - Page Nine This is his Lymphocyte Sensitivity Test result: Finally, the test results of a young woman with MS (ex smoker), also living in the flight path of jet-liners and near the same international airport mentioned above, which makes me wonder about chemical trails: The Nitrosamine adduct is located this time on the PPARG gene. Page Ten My closing comment when considering the article submitted by Dr. Plumb is just this: We have been schooled to believe that toxic metals are problematic…. When I review the test results I’ve enclosed, it appears that far more than toxic metals is exerting epigenetic and carcinogenic effects on man. The WTC was a devastating event – trauma abounded, but what indeed WAS in that lethal cocktail that filtered down that day when the two jet-liners crashed into the Twin Towers of the WTC? Limited Bibliography Dai, Q. (1998), Di-Region Theory , New Discovery on Mechanism of Carcinogenesis, Molecular Engineering, 8, 61-89. California Department of Public Health, 2010c. NDMA and Other Nitrosamines. Online: http://www.cdph.ca.gov/certlic/drinkingwater/Pages/NDMA.aspx [accessed 7 January 2010] ATSDR (Agency for Toxic Substances and Disease Registry). 1989. Toxicological profile for Nnitrosodimethylamine. Prepared by the Syracuse Research Corporation for ATSDR in collaboration with the U.S. Environmental Protection Agency. U.S. Public Health Service, Washington, D.C. 119 pp. Kind regards Carin S. Smit M/CMT South Africa