Anti-C8G monoclonal antibody, clone 056B-373

The spectrum of mutations induced by N-acetoxy-N-acetyl-2-aminofluorene (N-AcO-AAF) was examined by the pZipHprtNeo shuttle vector in mammalian cells. The vector carries a cDNA of the human hypoxanthine phosphoribosyl transferase (hprt) gene, which is stably integrated into chromosomal DNA of a mouse cell line, VH12. After treatment of the cell with N-AcO-AAF, 48 independent 6-thioguanine-resistant clones were obtained and altered sequences of the mutated cDNA hprt genes were determined. Frameshifts and deletions were the predominant mutational events (68%) induced by N-AcO-AAF and the remainder were base substitutions (32%) of various types. Analysis of sequence alterations at all the sites of mutation revealed that: (i) > 65% of mutations occurred at G:C sites, suggesting C8G adducts are responsible premutagenic lesions for these mutations; and (ii) short sequence repeats were frequently found at the sites of frameshift and deletion, and slippage-misalignment is the suggested mechanism for the induction of mutations at these sites. Implied significance of slippage-misalignment as a fundamental mechanism for mutagenesis is discussed.

P>Variants in the genes of the alternative complement pathway are associated with risk of numerous inflammatory diseases. Abdominal aortic aneurysm is associated with inflammation and is a common cause of illness and death among European populations. This study tested 49 single nucleotide polymorphisms, including common putatively functional polymorphisms, in the genes of the alternative complement cascade (CFH, CFB, CFD, CFI, properdin, CR1, CR1L, CR2, CD46, vitronectin, C3, C5, C6, C7, C8A, C8B, C8G and C9). The study group were 434 cases with infra-renal aortic diameter >= 30 mm and 378 disease-free controls from two UK centres, all with self-reported European ancestry. There was no evidence for significant association with presence or size of aneurysm following correction for multiple testing. This study suggests that variation in the genes of the alternative pathway is not an important cause of abdominal aortic aneurysm development.