The alkylation of DNA by racemic 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) exhibits a strong preference for formation of trans adducts between the N2 deoxyguanosine alkylation site and the (+)-enantiomer of anti-BPDE. In the presence of 10 mM buffer with no added salt, 98% of the adducts formed with native calf thymus DNA result from trans opening of the epoxide ring. The strong selectivity for trans adduct formation obtained with duplex DNA at low salt concentration is found to a lesser degree with poly(G) but is nearly absent with dAMP. When DNA adducts are formed in 10 mM MgCl2 or 1 M NaCl, the proportion of cis adducts increases to approximately 7 and approximately 26%, respectively. At low salt, 10 mM MgCl2, and 1 M NaCl, deoxyguanosine adducts are approximately 1%, 6%, and 24% cis, whereas deoxyadenosine adducts are approximately 11%, 14%, and 37% cis, respectively. NaCl also increases the proportion of cis adducts formed with poly(G) and dAMP. It is proposed that the increase in cis-adduct formation due to salt results from SN1 attack of chloride ion on the BPDE carbocation, forming a trans chlorohydrin, followed by SN2 attack of DNA.

The International Knockout Mouse Consortium (IKMC) developed high throughput gene trapping and gene targeting pipelines that produced mostly conditional mutations of more than 18,500 genes in C57BL/6N mouse embryonic stem (ES) cells which have been archived and are freely available to the research community as a frozen resource. From this unprecedented resource more than 6,000 mutant mouse strains have been produced by the IKMC and mostly the International Mouse Phenotyping Consortium (IMPC). In addition, a cre-driver resource was established including 250 inducible cre-driver mouse strains in a C57BL/6 background. Complementing the cre-driver resource, a collection of comprising 27 cre-driver rAAVs has also been produced. The resources can be easily accessed at the IKMC/IMPC web portal (www.mousephenotype.org). The IKMC/IMPC resource is a standardized reference library of mouse models with defined genetic backgrounds that enables the analysis of gene-disease associations in mice of different genetic makeup and should therefore have a major impact on biomedical research.