Quantification of skin erythema response to topical alcohol in alcohol-intolerant East Asians.

BACKGROUND/PURPOSE: Severe alcohol intolerance characterized by flushing, headache, nausea, and tachycardia even after very modest oral alcohol consumption, is common among East Asians (Chinese, Japanese, Koreans) and has been associated with the accumulation of acetaldehyde resulting from genetic polymorphism of aldehyde dehydrogenase (ALDH). These individuals also display erythema of the skin in response to exposure to topical alcohol. We have recently observed that dietary phytochemicals such as sulforaphane can accelerate the disposal of acetaldehyde from cells and animals by inducing ALDH. The goal of this study was to quantify the erythema response of skin to topical alcohol exposure. METHODS: The erythema response of the forearm skin of healthy Japanese with unusual alcohol sensitivity evoked by a range of very low doses of alcohol (2, 4, 8, and 16 µmol/cm2 ) was determined by means of a chromometer, which measures a* values (red-green scale). RESULTS: The magnitude of the a* response (∆a*) to alcohol was time- and dose-dependent, but differed considerably among individuals. It was much higher in those individuals who claimed to be alcohol intolerant, and ∆a* was unrelated to the initial a* values of the skin prior to alcohol challenge. CONCLUSION: The ∆a* index is suitable for the quantitative determination of topical alcohol-induced erythema response, and the evaluation of effectiveness of protective strategies against erythema response.

Mutation analysis of hBUB1 in aneuploid HNSCC and lung cancer cell lines.

Aneuploidy is frequently observed in many types of human cancer cells, suggesting that mutations of genes required for chromosomal stability may occur in human tumors. The BUB gene is a component of the mitotic checkpoint in budding yeast that delays anaphase in the presence of spindle damage thus increasing the probability of successful delivery of a euploid genome to each daughter cell. Recently, human homologues of the BUB gene were identified and mutant alleles of hBUB1 were detected in two colorectal tumor cell lines. Transfection of one mutant allele led to dominant disruption of the mitotic checkpoint control in a euploid cell, suggesting that aneuploidy in some tumors could be due to defects in the mitotic checkpoint. We analyzed the entire coding sequence of hBUB1 for mutation in 31 head and neck squamous cell carcinoma (HNSCC) and lung cancer cell lines, most with severe aneuploidy. We found expression of the hBUB1 gene in all cell lines and only a single nucleotide substitution in one cell line without a resultant change in amino acid sequence. Our study demonstrates that hBUB1 is rarely a target for genetic alterations in tumors of the respiratory tract.

Serial analysis of gene expression in non-small cell lung cancer.

We used the serial analysis of gene expression (SAGE) method to systematically analyze transcripts present in non-small cell lung cancer. Over 226,000 SAGE tags were sequence analyzed from two independent primary lung cancers and two normal human bronchial/tracheal epithelial cell cultures. A total of 226,000 SAGE tags were sequence identified, representing 43,254 unique transcripts. Comparison of the tags present in the tumor with those identified in the normal tissue revealed 175 transcript tags that were overrepresented in the normal tissue and 142 tags that were overexpressed in the tumor by 10-fold or more. Northern hybridization was performed on 15 of the most abundantly expressed tags identified in the tumors. These tags were derived from either a known gene or a matched expressed sequence tag clone. The transcripts for 3 of the 15 genes, PGP 9.5, B-myb, and human mutT, were abundantly expressed in primary lung cancers (10 of 18, 15 of 18, and 6 of 12 tumors, respectively). In contrast, the presence of PGP9.5 and B-myb was much less frequent in primary tumors derived from other tissue origins. These results suggest that at least a portion of the transcripts identified by SAGE are frequently associated with lung cancer, and that their overexpression may contribute to lung tumorigenesis. The identification and further characterization of genes generated by SAGE should provide potential new targets for the diagnosis, prognosis, and therapy of lung cancer.