['Group', 'No.', 'Dogs', 'High', 'nicotine', 'cigarette,', 'low', 'dose', '60', 'High', 'nicotine', 'cigarette,', 'high', 'dose', '60', 'Low', 'nicotine', 'cigarette,', 'low', 'dose', '60', 'Low', 'nicotine', 'cigarette,', 'high', 'dose', '60', 'Sham-smoked', 'controls', '30', '6.', 'Conduct', 'routine', 'and', 'special', 'in', 'vivo', 'tests', 'in', 'accordance', 'with', 'the', 'RFP', 'and', 'the', "Contractor's", 'proposal', 'referenced', 'below.', '7.', 'Conduct', 'post-sacrifice', 'examination', 'in', 'accordance', 'with', 'the', 'RFP', 'and', 'the', "Contractor's", 'proposal.', '8.', 'Report', 'on', 'in', 'vivo', 'and', 'post', 'mortem', 'manifestations', 'which', 'may', 'be', 'attributable', 'to', 'nicotine,', 'evaluate', 'the', 'quantitative', 'effect', 'of', 'nicotine', 'as', 'far', 'as', 'possible,', 'and', 'discuss', 'lowered', 'nicotine', 'as', 'a', 'factor', 'in', 'development', 'of', 'less-hazardous', 'cigarettes.', '9.', 'Report', 'on', 'the', 'pathogenesis', 'of', 'response', 'to', 'cigarette', 'smoke,', 'tumorigenic', 'and', 'otherwise;', 'early', 'signs,', 'progress,', 'relationship', 'between', 'different', 'mani-', 'festations.', '10.', 'Report', 'on', 'equipment,', 'materials', 'and', 'techniques;', 'recommend', 'standard', 'operating', 'procedures', 'for', 'further', 'use', 'of', 'the', 'beagle', 'in', 'quantitative', 'bioassays;', 'and', 'recommend', 'developments', 'to', 'advance', 'the', 'state-', 'of-the-art.', 'RATIONALE:', 'To', 'study', 'further', 'health', 'effects', 'of', 'nicotine', 'in', 'the', 'beagle,', 'The', 'project', 'will', 'study', 'carcinogenesis', 'and', 'other', 'effects', 'of', 'cigarette', 'smoke.', 'In', 'vivo', 'pul-', 'monary', 'and', 'metabolic', 'tests', 'will', 'be', 'conducted.', 'Post', 'mortem', 'examination', 'will', 'determine', 'the', 'site', 'of', 'pulmonary', 'neoplasias,', 'other', 'effects,', 'and', 'cardio-', 'vascular', 'changes', 'especially', 'in', 'myocardial', 'arterioles', 'will', 'be', 'sought.', 'Nicotine', 'is', 'important', 'because', 'its', 'concentration', 'in', 'smoke', 'condensate', 'correlates', 'with', 'tumorigenicity', 'in', 'mouse', 'skin', 'painting.', 'It', 'has', 'also', 'been', 'implicated', 'in', 'various', 'cardiovascular', 'effects.', '_TIMN', '422299']