a database of the National Library of M

in vivo. [Barbin A; IARC 150: 303-13 (1999)]**PEER REVIEWED**Ethenobases are exocyclic adducts formed with DNA by some environmentalcarcinogens such as vinyl chloride or urethane. ... Increased levels ofDNA etheno adducts have been measured in target tissues from rodentsexposed to vinyl chloride or urethane. Hepatic tumours caused by exposureto vinyl chloride in humans & in rats & lung tumours induced byurethane in mice exhibit base pair substitution mutations in the ras &p53 genes which seem to be exposure-specific & consistent with thepromutagenic properties of ethenobases. Background levels of ethenoadducts have been detected in DNA from non-exposed humans or animals,pointing to an alternative, endogenous pathway of formation. Thisbackground may be affected by dietary factors. It could arise from thereaction of trans-4-hydroxy-2-nonenal (or its epoxide2,3-epoxy-4-hydroxynonanal), a lipid peroxidation product, with nucleicacid bases. Elevated levels of etheno adducts are found in hepatic DNAfrom humans & rodents with genetic predisposition to oxidative stressand lipid peroxidation in the liver, & with an associated increasedrisk of liver cancer. These data suggest that DNA ethenobases could serveas new biomarkers of oxidative stress/lipid peroxidation. [Barbin A; ActaBiochim Pol 45 (1): 145-161 (1998)]**PEER REVIEWED**Previous studies have shown that a high proportion (5/6) of human liverangiosarcomas (ASL) associated with exposure to vinyl chloride (VC)contains a GC-- > AT mutation at the Ki-ras codon 13. This mutation,however, has not been found in 5 ASL or 2 hepatocellular carcinomas (HCC)induced in rats by VC. These 2 HCC did contain a mutation at codon 61 ofthe Ha-ras gene. In order to extend this study & further explore themechanisms of tumour induction, an addl 6 ASL & 6 HCC induced in ratsby VC were analysed for ras gene point mutations, as well as 10 rat &10 murine ASL induced by vinyl fluoride (VF), & 5 ASL, 6 Kupffer cellsarcomas, 4 HCC & 2 cholangiocellular carcinomas induced by Thorotrastin rats. Tumour DNA was analysed by PCR-SSCP & direct sequencing. Noneof the rodent ASL contained a mutation at codon 13 of the Ki-ras geneshowing that the ras gene mutational pattern is species-specific. TheCAA-- > CTA mutation, previously found at codon 61 of the Ha-ras gene inrat HCC, was observed in 5 further VC-induced HCC but was not detected inthe Thorotrast-induced HCC, suggesting carcinogen-specificity. Thismutation was also absent in VC-induced ASL, which supports thecell-specificity of the ras mutational pattern in chemically inducedtumours. No predominant mutation was detected in VF- &Thorotrast-induced tumours. Thus, a given mutation in a tumour may becarcinogen-specific but also depend on the species & the cell type.[Boivin-Angele S et al; Int J Cancer 85 (2): 223-227 (2000)]**PEERREVIEWED**Vinyl chloride is a known human & animal carcinogen that inducesangiosarcomas of the liver. /The authors/ review here studies on theformation & repair of DNA adducts associated with vinyl chloride &vinyl fluoride in exposed & control rodents & unexposed humans.These vinyl halides induce etheno (epsilon) adducts that are identical tothose formed after lipid peroxidation. Of these adducts,N2,3-ethenoguanine (epsilon G) is present in greatest amounts in tissuesof exposed animals. After exposure to vinyl chloride for four weeks,epsilon G levels attain steady-state concns, such that the amount of newlyformed adducts equals the number of adducts that are lost each day. Wereport the first dosimetry of epsilon G in rats exposed to 0, 10, 100 or