Induction of cyclin D1 by arsenite and UVB-irradiation in human keratinocytes.

Arsenic is an environmental pollutant with carcinogenic properties that is found in many regions of the world but that poses a health risk primarily in economically disadvantaged areas. In these areas, arsenic ingestion affects various tissues, especially skin in which it acts as a comutagen with the ultraviolet component of solar radiation. Both epidemiological and experimental evidence indicates that arsenic and ultraviolet radiation act on signaling pathways that effect the expression of cyclin D1.

Spectrum of mitochondrial DNA deletions within the common deletion region induced by low levels of UVB irradiation of human keratinocytes in vitro.

We show that a single low-dose exposure of human epidermal keratinocytes (NHEK) to an FS20 light source in vitro can induce the formation of mitochondrial DNA deletions in a PCR detection assay. We used primer sets specifically designed to exclude amplification of segments containing the common deletion, but which could detect possibly lower abundance deletions generated within the same region of the mitochondrial genome. We characterized eight novel deletions of which six were generated from cut sites within, or adjacent to, short direct repeats.

Patterns of persistent DNA damage associated with sun exposure and the glutathione S-transferase M1 genotype in melanoma patients.

Solar radiation can lead to changes affecting DNA metabolism resulting in loss of DNA integrity. Skin specimens obtained from melanoma patients treated at the Memorial Sloan-Kettering Cancer Center were used to study patterns of DNA fragmentation using the comet assay and levels of deletions in mitochondrial DNA (mtDNA) using real-time PCR. Skin specimens were classified according to the glutathione S-transferase M1 (GSTM1) genotype (either wild type [WT] or null) and patient sunburn history.

E-cadherin gene alterations in gastric cancers in different ethnic populations.

Introduction: A retrospective study of nucleotide sequence alterations in exons 7-9 of the E-cadherin gene and expression of E-cadherin and beta-catenin in gastric tumors from African American, Asian, Causcasian and Hispanic patients was carried out to determine differences potentially related to race/ethnicity in these groups.

Methods: Paraffin-embedded tissue sections archived at the Memorial Sloan Kettering Cancer Center were used for immunohistochemical staining of sections for membranous E-cadherin protein and nuclear localization of beta-catenin. DNA from tumor tissue extracted from the paraffin sections was used as template for amplification of the E-cadherin gene exonic regions.

Mitochondrial DNA deletions in skin from melanoma patients.

We measured the cellular levels of two types of mitochondrial DNA (mtDNA) deletions--the 4977-bp common deletion and recently identified UVB-induced deletion of 5128 bp--in apparently normal skin obtained from wide excisions in melanoma patients. The number of deleted mtDNAs as well as the total mtDNA copy number was highly variable, but the number of deletions increased with age of the donor almost 12-fold across the age range of the patients. Patients were scored for degree of overall pigmentation and response to sunlight by a phenotypic index (PI).