There are over 4000 chemical compounds in secondhand smoke; 200 of which are known to be poisonous, and upwards of 60 have been identified as carcinogens. Exposure to secondhand smoke or even just a past smoking history can also increase the likelihood of bladder cancer in offspring. One of the most commonly used antineoplastic agents for the treatment of advanced bladder cancer is cisplatin, but the development of resistance to cisplatin during treatment is common and constitutes a major obstacle to the cure of sensitive tumors. Although many studies have been conducted on the molecular mechanism of drug resistance, little is known about the treatment of these drug-resistant tumors, which still remains a significant problem. A number of reports have suggested that cancer patients who smoke while receiving treatment have poorer TMS outcomes compared with their nonsmoking counterparts, possibly because of lower rates of response. Retrospective series of patients with renal, bladder, and TMI 1 especially glottic cancers also indicate a link between smoking during treatment and decreased efficacy of cancer therapies. However, there are no direct data showing that cigarette smoke could actually induce resistance to chemotherapeutic agents, such as cisplatin. Deletion of chromosome 9p frequently occurs in bladder tumors. Depending on the respective investigation, frequencies between 30 and 70% have been published. Studies by Blaveri et al., indicate that in primary bladder cancer, loss of clones across the entire chromosome 9 occurs with an average frequency of 47% for 9p and 46% for 9q. Chromosome 9 carries important genes involved in adenine metabolism, namely AK1, AK2 and AK3. All three AKs are nuclear-encoded proteins and synthesized in the cytoplasm. AK1 remains located mainly in the cytosol of different tissues. Mature AK2 and AK3 are imported into mitochondria, where AK2 resides in the intermembrane space whereas AK3 is located exclusively in the mitochondrial matrix. Cigarette smoke is also known to induce mitochondrial damage as well as dysfunction which may in turn increase cisplatin resistance in bladder cancer cells. In this study we examined the relationship between tobacco exposure and cisplatin resistance in relation to mitochondria function and specifically to a mitochondria-resident protein AK3.