a database of the National Library of M

N-5'-alkylpurine (AP) endonucleases. The enzyme incises such oligomers 5'to the adduct & generates 3'-hydroxyl & 5'-phosphoryl termini butleaves the modified base on the 5'-terminus of the 3' cleavage fragment('dangling base'). Using active-site mutants of the human AP endonuclease,we found that the active site for the primary substrate, abasic (AP) site,is the same as that for the bulky pBQ adducts. There appears to be noclear rationale for the widely differing recognition & repairmechanisms for these exocyclic adducts, as shown for the repair of thesame types of modification on different bases (e.g. epsilon A &epsilon C) & for completely unrelated lesions (e.g. AP site & pBQadducts). Another important variable that affects the rate & extent ofrepair is the effect of neighbouring bases. In the case of epsilon A, thissequence-dependent repair correlates with the extent ofdouble-strandedness of the substrate, as demonstrated by thermal stabilitystudies. [Singer B et al; IARC Sci Publ 150: 233-247 (1999)]**PEERREVIEWED**The production of mutations in cellular tumor suppressor genes such as p53is involved in the development of many human cancers. These mutationsresult in the expression of mutant forms of the encoded p53 protein whichcan potentially serve as a biomarker for this carcinogenic process.Workers exposed to vinyl chloride who are at risk for the development ofthe sentinel neoplasm angiosarcoma of the liver represent a modelpopulation for the study of such a mutant p53 biomarker, since vinylchloride is known to cause specific p53 mutations in persons withangiosarcoma of the liver. To determine the relation between vinylchloride exposure & this p53 biomarker, the authors examined serumsamples collected between 1987 & 1992 from a cohort of 225 Frenchvinyl chloride workers & 111 unexposed controls (matched according toage, sex, race, smoking, & alcohol drinking) for the presence ofmutant p53 protein, using an enzyme-linked immunosorbent assay.Stratification of the exposed workers by quartile of vinyl chlorideexposure (in estimated ppm-yr) yielded a statistically significant trendof increasing odds ratios for p53 biomarker seropositivity with increasingexposure. These results suggest that this serum biomarker for mutant p53protein is related to vinyl chloride exposure & may be an earlyindicator of carcinogenic risk in exposed individuals. [Smith SJ et al; AmJ Epidemiol 147 (3): 302-308 (1998)]**PEER REVIEWED**Vinyl chloride (VC) is a known animal & human carcinogen that isassociated with liver angiosarcoma & most likely also withhepatocellular carcinoma (HCC) in humans. The authors examined thepresence of p53 gene mutations in 18 HCC specimens from patients withknown exposure to VC (median, 8883 ppm-yr; median duration, 245 months).In all cases, other risk factors for the development of HCC (hepatitis Bvirus & hepatitis C virus infections, alcohol consumption, &metabolic or autoimmune disorders) were excluded. Three patients hadconcomitant cirrhosis. The p53 gene was examined by direct sequencing ofexons 5-9. Mutations of the p53 gene were found in 11 of 18 HCCs examined.The point mutations detected were comprised of five transversions &five transitions. Five of 11 mutations (codons 175, 245, 248, 273, &282) occurred at CpG sites. Histopathologic liver alterations (mildsinusoidal dilatation, [portal] fibrosis, & centrilobular siderosis)in tumor surrounding nonneoplastic liver confirmed exposure to VC. Theresults of the current study indicated a relation between VC exposure& the development of HCC. The mutation pattern of p53 with a nearlyequal rate of incidence of transitions & transversions & a high