TY - JOUR
T1 - Cloning of the human aflatoxin B1-aldehyde reductase gene at 1p35- 1p36.1 in a region frequently altered in human tumor cells
AU - Praml, Christian
AU - Savelyeva, Larissa
AU - Perri, Patrizia
AU - Schwab, Manfred
PY - 1998/11/15
Y1 - 1998/11/15
N2 - Alterations of the distal portion of the short arm of chromosome 1 (1p) are among the earliest abnormalities of human coloroctal tumors. Loss of heterozygosity analysis has previously revealed a smallest region of overlapping deletion (SRO) B, at 1p35-36.1, deleted in 48% of sporadic tumors. From this region we have now cloned a gene encoding a protein of 330 amino acids that is 78% identical with the Rattus norvegicus aflatoxin B1 aldehyde reductase (Afar) and, therefore, likely represents its human homologue. In rat liver, Afar is strongly inducible by the antioxidants ethoxyquin and butylated hydroxyanisole, which protect the rat against aflatoxin B1-induced liver tumorigenesis by detoxifying its genotoxic and cytotoxic dialdehyde. Human AFAR is expressed in a broad range of tissues and, therefore, is likely involved in endogenous detoxication pathways. Impaired detoxication of genotoxic aldehydes and ketones, which are involved in tumorigenesis of the colon and breast, may be a crucial factor both for tumor initiation and progression. We here provide a detailed contig of 1.5-2 Mbp/2.7 cM encompassing part of SRO B, including known genes and previously unmapped expressed sequence tags. PLA2G2A (secretory type II phospholipase A2), described previously as a candidate, is localized outside SRO B.
AB - Alterations of the distal portion of the short arm of chromosome 1 (1p) are among the earliest abnormalities of human coloroctal tumors. Loss of heterozygosity analysis has previously revealed a smallest region of overlapping deletion (SRO) B, at 1p35-36.1, deleted in 48% of sporadic tumors. From this region we have now cloned a gene encoding a protein of 330 amino acids that is 78% identical with the Rattus norvegicus aflatoxin B1 aldehyde reductase (Afar) and, therefore, likely represents its human homologue. In rat liver, Afar is strongly inducible by the antioxidants ethoxyquin and butylated hydroxyanisole, which protect the rat against aflatoxin B1-induced liver tumorigenesis by detoxifying its genotoxic and cytotoxic dialdehyde. Human AFAR is expressed in a broad range of tissues and, therefore, is likely involved in endogenous detoxication pathways. Impaired detoxication of genotoxic aldehydes and ketones, which are involved in tumorigenesis of the colon and breast, may be a crucial factor both for tumor initiation and progression. We here provide a detailed contig of 1.5-2 Mbp/2.7 cM encompassing part of SRO B, including known genes and previously unmapped expressed sequence tags. PLA2G2A (secretory type II phospholipase A2), described previously as a candidate, is localized outside SRO B.
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M3 - Article
C2 - 9823300
AN - SCOPUS:0032533855
VL - 58
SP - 5014
EP - 5018
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 22
ER -