Showing papers by "Ahmad Besaratinia published in 2008"

Second-hand smoke and human lung cancer

Abstract: Since the early 1980s, there has been growing concern about potential health consequences of exposure to second-hand smoke (SHS). Despite SHS being established as a risk factor for lung cancer development, the estimated risk has remained small yet somehow debatable. Human exposure to SHS is complicated because of temporal variabilities in source, composition, and concentration of SHS. The temporality of exposure to SHS is important for human lung carcinogenesis with a latency of many years. To explore the causal effect of SHS in lung carcinogenesis, exposure assessments should estimate chronic exposure to SHS on an individual basis. However, conventional exposure assessment for SHS relies on one-off or short-term measurements of SHS indices. A more reliable approach would be to use biological markers that are specific for SHS exposure and pertinent to lung cancer. This approach requires an understanding of the underlying mechanisms through which SHS could contribute to lung carcinogenesis. This Review is a synopsis of research on SHS and lung cancer, with special focus on hypothetical modes of action of SHS for carcinogenesis, including genotoxic and epigenetic effects.

Rapid repair of UVA-induced oxidized purines and persistence of UVB-induced dipyrimidine lesions determine the mutagenicity of sunlight in mouse cells

Abstract: Despite the predominance of ultraviolet A (UVA) relative to UVB in terrestrial sunlight, solar mutagenesis in humans and rodents is characterized by mutations specific for UVB. We have investigated the kinetics of repair of UVA- and UVB-induced DNA lesions in relation to mutagenicity in transgenic mouse fibroblasts irradiated with equilethal doses of UVA and UVB in comparison to simulated-sunlight UV (SSL). We have also analyzed mutagenesis-derived carcinogenesis in sunlight-associated human skin cancers by compiling the published data on mutation types found in crucial genes in nonmelanoma and melanoma skin cancers. Here, we demonstrate a resistance to repair of UVB-induced cis-syn cyclobutane pyrimidine-dimers (CPDs) together with rapid removal of UVA-induced oxidized purines in the genome overall and in the cII transgene of SSL-irradiated cells. The spectra of mutation induced by both UVB and SSL irradiation in this experimental system are characterized by significant increases in relative frequency of...

Sunlight ultraviolet irradiation and BRAF V600 mutagenesis in human melanoma

Abstract: The incidence of melanoma, the most lethal form of skin cancer, continues to increase in the Western world. In addition to genetic alterations in high- and low-susceptibility genes identified for melanoma, somatic mutations in BRAF gene occur frequently in human melanoma and are distinctively linked to sun exposure. Of significance is a single hotspot codon, i.e., BRAF V600, wherein up to 92% of all mutations arise. Recent work in our laboratory has demonstrated that solar ultraviolet (UV) irradiation triggers mutagenesis through induction of various DNA lesions, many of which capable of producing similar types of mutations, as those seen in BRAF V600 variants in human melanoma. In this review article, we have discussed application of “DNA damage-targeted mutagenicity” of solar UV-irradiation for determining the mechanistic involvement of sunlight UV in BRAF V600 mutagenesis in human melanoma. We envision that establishing “DNA-damage derived mutagenesis” in this exceptionally unique target gene may resolve the underlying mechanism(s) of melanoma-genesis, thus helping define preventive and therapeutic measures against this malignant disease. Hum Mutat 0, 1–9, 2008. © 2008, Wiley-Liss, Inc.