[' ', ' ', 'IDENTIFYING', 'NO.:', '5P01CA29580-13', '0006', 'AGENCY', 'CODE:', 'CRISP', 'ANALYTICAL', 'STUDIES', 'IN', 'TOBACCO', 'CARCINOGENESIS', 'PRINCIPAL', 'INVESTIGATOR:', 'BROUNNEMANN,', 'KLAUS', 'D', 'ADDRESS:', 'AMERICAN', 'HEALTH', 'FOUNDATION', 'ONE', 'DANA', 'ROAD', 'VALHALLA,', 'NEW', 'YORK,', '10595', 'PERFORMING', 'ORG.:', 'AMERICAN', 'HEALTH', 'FOUNDATION,', 'VALHALLA,', 'NEW', 'YORK', 'SPONSORING', 'ORG.:', 'NATIONAL', 'CANCER', 'INSTITUTE', 'FY', ':', '94', '‘TYPE', 'OF', 'AWARD:', 'Noncompeting', 'Continuation', '(Type', '5)', 'SUMMARY:', 'The', 'major', 'goal', 'of', 'this', 'project', 'is', 'to', 'give', 'new', 'directives', 'for', 'studies', 'in', 'tobacco', 'carcincgenesis', 'by', 'identifying', 'potential', 'carcinogens', 'in', 'smokelasa', 'tobacco,', 'mainstream', 'and', 'sidestream', 'cigarette', 'smoke,', 'and', 'environmental', 'tobacco', 'smoke', '{ERS}', 'As', 'in', 'the', 'past,', 'newly', 'identified', '’', 'assessed,', 'their', 'formation', 'has', 'to', 'be', 'studied', 'and', 'they', 'must', 'be', 'assayed', 'in', 'vitro', 'and/or', 'in', 'vivo', 'for', 'tumorigenicity.', 'We', 'plan', 'to', 'investigate', 'N-nitrosamino', 'acids', 'in', 'chewing', 'tobacco', 'and', 'to', 'examine', 'their', 'carcinogenic', 'activity.', 'We', 'will', 'also', 'study', 'the', 'fate', 'of', 'N-nitrosamino', 'acids', 'during', 'cigarette', 'amoking.', 'The', 'significant', 'carcinogenic', 'activities', 'of', 'some', 'naltroalkanes,', 'nitroalkenea,', 'and', 'protein-derived', 'heterocyclic', 'amines', 'make', 'it', 'highly', 'desirable', 'to', 'assay', 'these', 'pyrolysis', 'products', 'in', 'tobacco', 'smoke.', 'Wa', 'will', 'develop', 'new', 'analytical', 'methods', 'on', 'the', 'basis', 'of', 'aupercritical', 'fluid', 'extraction', '(SFE)', 'and', 'GC-MS.', '3-vinylpyridine,', 'a', 'pyrolysis', 'product', 'of', 'the', 'Nicotiana', 'alkaloids,', 'will', 'be', 'assayed', 'as', 'a', 'marker', 'that', 'is', 'well', 'suited', 'to', 'determine', 'the', 'contribution', 'of', 'volatile', 'tobacco', 'smoke', 'constituents', 'to', 'indoor', 'air', 'pollution.', 'This', 'far,', 'only', 'nicotine', 'has', 'been', 'used', 'as', 'marker', 'for', 'ETS,', 'but', '@', 'xeliable', 'indicator', 'for', 'volatile', 'gnoke', 'earcinogens', 'in', 'ETS', 'is', 'urgently', 'needed.', '3-Vinylpyridine', 'appears', 'to', 'suitable', 'for', 'this', 'purpose,', 'since', 'unlike', 'nicotine', 'it', 'remains', 'static', '3', 'the', 'polluted', 'air', 'over', 'a', 'period', 'of', 'several', 'hours.', 'We', 'have', 'identified', '4-(methylnitrosamino)', '—4-(3-pyridyl)', 'butyric', 'acid', '(ise-', 'NNAC)', 'in', 'smokeless', 'tobacco,', 'but', 'did', 'not', 'find', 'it', 'in', 'tobacco', 'smoke.', 'Since', 'iso-NNAC', 'can', 'be', 'a', 'nitrosation', 'product', 'of', 'nicotine', 'and/or', 'its', 'metabolites,', 'and', 'asaince', 'it', 'is', 'not', 'carcinogenic', 'and', 'is', 'excreted', 'in', 'the', 'urine', 'without', 'undergoing', 'metabolism,', 'it', 'may', 'serve', 'as', 'a', 'marker', 'for', 'the', 'endogenous', 'formation', 'of', 'tobacco-specific', 'N-nitrosamines', '(TSNA)', 'in', 'the', 'urine', 'of', 'smokers.', 'It', 'is', 'likely', 'that', 'Nicotiana', 'alkaloids', 'inhaled', 'by', 'the', 'smoker', 'are', 'potential', 'precursors', 'to', 'endogenously', 'formed', 'carcinogenic', 'TSNA,', 'Therefore,', 'an', 'da-dept', 'bh', 'analytical', 'study', '1s', 'proposed', 'to', 'determine', '1s0-NNAC', 'in', 'the', 'urine', 'of', 'amokers.', 'Epidemiological', 'studies', 'have', 'demonstrated', 'an', 'increased', 'risk', 'for', 'eigarette', 'amckera', 'for', 'cancer', 'of', 'the', 'uterine', 'cervix.', 'Nicotine', 'and', 'cotinine', 'as', 'well', 'as', 'nitrite', 'have', 'been', 'identified', 'in', 'cervical', 'mucus;', 'it', 'is', 'likely', 'therefore,', 'that', 'carcinegenic', 'TSNA', 'can', 'be', 'formed', 'in', 'the', 'cervical', 'vault', 'of', 'cervical', 'mucus.', 'We', 'plan', 'to', 'explore', 'this', 'question', 'by', 'analyzing', 'the', 'cervical', 'mucus', 'of', 'cigarette', 'smokers', 'and', 'nonsmokers.', 'The', 'xesults', 'of', 'this', 'project', 'will', 'answer', 'important', 'questions', 'in', 'tobacco', 'carcinogenesis', 'and', 'will', 'give', 'impetus', 'to', 'new', 'biochemical', 'atudies', 'in', 'chemical', 'and', 'environmental', 'carcinogenesis.', '6/7/743', 'DIALOG(R)File', '266:Fed.', 'Res.', 'in', 'Progreas', '(c)', 'format', 'only', '1995', 'Dialog', 'Info.Sves.', 'All', 'rts.', 'reserv.', '0216844', 'IDENTIFYING', 'NO.:', '5P01CA29580~13', '0001', 'AGENCY', 'CODE:', 'CRISP', 'PERFORMIN:', '[2G.;', 'AMERICAN', 'HEALTH', 'FOUNDATION,', 'VALHALLA,', 'NEW', 'YORK', 'SPONSORING', 'ORG.:', 'NATIONAL', 'CANCER', 'INSTITUTE', 'FY', ':', '94', 'TYPE', 'OF', 'AWARD:', 'Noncompeting', 'Continuation', '(Type', '5)', 'L66¢C', 'OPTTS', 'est', ' ']