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NF-B can repress p53 activity through upregulation of the p53 inhibitor MDM2 [73] Alternatively, the IB kinase (IKK), a major player in the canonical NF-B pathway, can induce post-translational modifications in the p53 protein, altering its stability [74] (Figure 4A)

According to an industry analysis in 1989, Sales of low tar brands have increased much more rapidly [in Italy] than in other European markets. The tar and nicotine issue culminated in some sense with the establishment of European standards, passed in 1990: the maximum allowable tar level in cigarettes would be set at 15 milligrams in 1992 and then decline to 12 in 1997