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Early efforts to alter the risks of cigarettes focused on reducing the yields of tar and nicotine as measured by machine-smoking methods.

Age-specific rates of lung cancer death, by gender and age group, in the United States and Australia,

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Some constituents of tobacco smoke or their metabolites may bind directly to cellular receptors, leading to activation of protein kinases, growth receptors, and other pathways, which can contribute to carcinogenesis Chen et al.

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Salgueiro L. If the DNA adducts produced by tobacco smoke carcinogens and their metabolites evade repair systems and remain, they can cause miscoding during DNA replication when bypass DNA polymerase enzymes direct the placement of an incorrect nucleobase opposite the adduct USDHHS
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