Worldwide Scientific Affairs Distribution 1998 To: Date: April Ocs tcc: Cathy Ellis From: source of toxic glycation products Subject: Review of "Tobacco smoke PNAS 94 13915-13920 (1992) Cerami et al claim havc   cstablished that both aqucous tobacco tobacco   smoke extracts allegc - condensate contain certain substances they call will rcact with protcins and glycotoxins " which thcy authors other cellular materials to form advanced glycation cnd products' (AGEs). The claim that AGE purported to higher in smokers. AGE formation contribute t0 the increased incidence of levels atherosclerosis and high prevalencc of cancer smokers: Detailed revicws of this publication were Ted Sanders (WSA Neuchatel) , Walter Hempfling received from Drs. Mingda Zhang (WSA Kongh, Hong (ReD Richmond) , and John Paine (RD Richmond) An executive summary is provided here. 'Other sources of " glycation products" ~linking  moieties that form from the Advanced  glycation end products (AGEs) are reactive CIOSS reaction of reducing sugars and the amino groups proteins, lipids defined by and nucleic acids, "glycotoxin" have been coined by the authors and are not well Cerami e al The tems "AGE" and accepted terms    However, sugars and proteins, lipids and nucleic acids are prevalent characterized likely control for dietary sources of "glycotoxins ' Food intake many foods and DO attempt was made reducing sugars and proteins relative provide least I00 times mOre obacco 'Lack of chemical plausibility The reaction of reducing sugars with amines has been known for least hundred ears and is nl This reaction, called the Maillard browning reaction, commonly occurs when food is cooked infomation: undergo The products of the Maillard reaction change baked: furher chemical and then condense Amadori products which are high lecular  weight polymers   that are  characterized by high Tesultin insolubility and Therefore reactivity. the authors suggesting these Obsenatons Teactve are the result of some other process Or chemical constitent: species AGE activity" be selectively filtered out of smoke supports the conclusion that The fact that the measured in these studies   Reducing sugars and similar compounds in Smoke being other substances are the particulate phase particulate phase components cannot be selectively removed: would reside and selectively filtered Only materials in the gas phase have the potential t0 be extremely labile" nature of the activity described by the authors provides additional evidence of The implausibility. If tobacco were to contain substances or their precursors that were as unstable in water as survive years of storage those described by Cerami they wouldn' tobacco processing and the distillation processes associated with smoke formation Therefore , the chemical combustion and behavior 1 Doc Code: P0622
Worldwide Scientific Affairs To: Distribution From: Cathy Ellis Ocs tcc: Subject: Review of "Tobacco smoke source of toxic glycation products PNAS 94 13915-13920 (1992) 1998 Date: April Cerami et al claim havc   cstablished that both aqucous tobacco extracts tobacco   smoke condensate contain certain substances they call glycotoxins " which thcy allegc - will rcact with protcins and other cellular materials to form advanced glycation cnd products' (AGEs). The authors claim that AGE levels higher in smokers. AGE formation purported to contribute t0 the increased incidence of atherosclerosis and high prevalencc of cancer smokers: Detailed revicws of this publication were received from Drs. Mingda Zhang (WSA Hong Kongh, Ted Sanders (WSA Neuchatel) , Walter Hempfling (ReD Richmond) , and John Paine (RD Richmond) An executive summary is provided here. 'Other sources of " glycation products" Advanced  glycation end products (AGEs) are reactive CIOSS ~linking  moieties that form from the reaction of reducing sugars and the amino groups proteins, lipids and nucleic acids, defined by Cerami e al The tems "AGE" and "glycotoxin" have been coined by the authors and are not well characterized accepted terms    However, sugars and proteins, lipids and nucleic acids are prevalent many foods and DO attempt was made control for dietary sources of "glycotoxins ' Food intake likely provide least I00 times mOre reducing sugars and proteins relative obacco 'Lack of chemical plausibility The reaction of reducing sugars with amines has been known for least hundred ears and is nl infomation: This reaction, called the Maillard browning reaction, commonly occurs when food is cooked baked: The products of the Maillard reaction undergo furher chemical change and then condense Tesultin Amadori products which are high lecular  weight polymers   that are  characterized by high insolubility and reactivity. Therefore Obsenatons the authors suggesting these Teactve species are the result of some other process Or chemical constitent: The fact that the AGE activity" be selectively filtered out of smoke supports the conclusion that other substances are being measured in these studies   Reducing sugars and similar compounds in Smoke would reside the particulate phase and particulate phase components cannot be selectively removed: Only materials in the gas phase have the potential t0 be selectively filtered The extremely labile" nature of the activity described by the authors provides additional evidence of implausibility. If tobacco were to contain substances or their precursors that were as unstable in water as those described by Cerami they wouldn' survive years of storage tobacco processing and the combustion and distillation processes associated with smoke formation Therefore , the chemical behavior 1 Doc Code: P0622