Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment - A Review.

Tobacco use is considered the single most important man-made cause of cancer that can be avoided. The evidence that nicotine is involved in cancer development is reviewed and discussed in this paper. Both tobacco smoke and tobacco products for oral use contain a number of carcinogenic substances, such as polycyclic hydrocarbons and tobacco-specific N-nitrosamines (TSNA), which undoubtedly contribute to tobacco related cancer.

Comparison of carcinogenic and in vivo genotoxic potency estimates.

Mutagenic substances classified as carcinogens are primarily regulated on the basis of their carcinogenic effect. Regulation of mutagens that have not been tested for carcinogenicity represents a problem. In cases where a threshold cannot be identified, the substances may be banned or if their uses are deemed to be unavoidable, the exposure may be reduced to as low as technically and economically feasible.

Comparison of carcinogen hazard characterisation based on animal studies and epidemiology.

Recently we have described a simple method for quantitative risk assessment of non-threshold carcinogens based on the dose descriptor T25. In the present report quantitative hazard estimates calculated with the T25 method have been compared with results obtained using quantitative methods based on epidemiological studies. "Known" and "Likely/Probably" human carcinogens were identified from the US EPA database IRIS.

Supplemental role of the Ames mutation assay and gap junction intercellular communication in studies of possible carcinogenic compounds from diesel exhaust particles.

This study presents a new strategy for the carcinogenic evaluation of complex chemical mixtures based on genotoxic and nongenotoxic assays. We studied the ability of organic extracts of diesel exhaust particles (DEP) to induce point mutations in five different Salmonella typhimurium strains (Ames test) and to inhibit gap junction intercellular communication (GJIC) in rat liver epithelial cell lines. A crude extract of DEP was prepared by extraction with dichloromethane (DCM), and fractionated according to polarity into five fractions: aliphatic hydrocarbons, polycyclic aromatic hydrocarbons (PAH), nitro-PAH, dinitro-PAH, and polar compounds.

Recovery of gap junctional intercellular communication after phorbol ester treatment requires proteasomal degradation of protein kinase C.

Reversible down-regulation of gap junctional intercellular communication (GJIC) is proposed to be an important cellular mechanism in tumor promotion. Gap junction function is modified by a variety of tumor promoters, including the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Treatment of cells with TPA results in the activation and subsequent depletion of the TPA-responsive protein kinase C (PKC) isoforms.

[Nicotine dependence--medico-biological aspects].

The nicotine in tobacco products is strongly addictive. This was generally recognised no earlier than in the late 1970s, though it was well known within the international tobacco industry in the early 1960s. Nicotine acts as an addictive substance by binding to acetylcholine receptors and causing the release of dopamine in the brain, though other signalling substances are also important for the action of nicotine in the central nervous system.