Using lysine adducts of human serum albumin to investigate the disposition of exogenous formaldehyde in human blood

Formaldehyde is a human carcinogen that readily binds to nucleophiles, including proteins and DNA. To investigate whether exogenous formaldehyde produces adducts in extracellular fluids, we characterized modifications to human serum albumin (HSA) following incubation of whole blood, plasma, and saliva with formaldehyde at concentrations of 1, 10 and 100 \u3bcM. The only HSA locus that showed the presence of formaldehyde modifications was Lys199. A N(6)-Lys adduct with added mass of 12 Da, representing a putative intramolecular crosslink, was detected in biological fluids that had been incubated with formaldehyde but not in control fluids. An adduct representing N(6)-Lys formylation was detected in all fluids, but levels did not increase above control values over the tested range of formaldehyde concentrations. An adduct representing N(6)-Lys199 acetylation was also measured in all samples. We then applied the assay to repeated samples of human plasma from 6 nonsmoking volunteer subjects (from Berkeley, CA), and single samples of serum from 15 workers exposed to airborne formaldehyde at about 1.5 ppm in a production facility and 15 control workers from Tianjin, China. Although all human plasma/serum samples contained basal levels of the products of N(6)-Lys formylation and acetylation, the putative crosslink product was not detected. Since the putative crosslink was observed in plasma incubated with formaldehyde at 1 \u3bcM, this suggests that the endogenous concentration of formaldehyde in serum was much lower than reported in the literature. Furthermore, concentrations of the formyl adduct were not higher in workers exposed to formaldehyde at about 1.5 ppm than in controls. Follow-up in vitro experiments with gaseous formaldehyde at 1.4 ppm detected the putative crosslink in plasma but not whole blood. This combination of results suggests that N(6) formylation occurs within cells with subsequent release of adducted HSA to the systemic circulation. Comparing across human samples, levels of N(6)-Lys199 formyl adducts were present at similar concentrations in subjects from California and China (about 1 mmol/mol HSA), but N(6)-Lys199 acetyl adducts were present at higher concentrations in Chinese subjects (0.34 vs. 0.13 mmol/mol HSA)

Large-scale evaluation of candidate genes identifies associations between DNA repair and genomic maintenance and development of benzene hematotoxicity.

Benzene is an established human hematotoxicant and leukemogen but its mechanism of action is unclear. To investigate the role of single-nucleotide polymorphisms (SNPs) on benzene-induced hematotoxicity, we analyzed 1395 SNPs in 411 genes using an Illumina GoldenGate assay in 250 benzene-exposed workers and 140 unexposed controls. Highly significant findings clustered in five genes (BLM, TP53, RAD51, WDR79 and WRN) that play a critical role in DNA repair and genomic maintenance, and these regions were then further investigated with tagSNPs. One or more SNPs in each gene were associated with highly significant 10-20% reductions (P values ranged from 0.0011 to 0.0002) in the white blood cell (WBC) count among benzene-exposed workers but not controls, with evidence for gene-environment interactions for SNPs in BLM, WRN and RAD51. Further, among workers exposed to benzene, the genotype-associated risk of having a WBC count 8-fold. In vitro functional studies revealed that deletion of SGS1 in yeast, equivalent to lacking BLM and WRN function in humans, caused reduced cellular growth in the presence of the toxic benzene metabolite hydroquinone, and knockdown of WRN using specific short hairpin RNA increased susceptibility of human TK6 cells to hydroquinone toxicity. Our findings suggest that SNPs involved in DNA repair and genomic maintenance, with particular clustering in the homologous DNA recombination pathway, play an important role in benzene-induced hematotoxicity

Host Plant Records for Fruit Flies (Diptera: Tephritidae: Dacini) in the Pacific Islands: 2. Infestation Statistics on Economic Hosts

Detailed host records are listed for 39 species of Bactrocera and 2 species of Dacus fruit flies, infesting 98 species of commercial and edible fruits in the Pacific Island Countries and Territories, based on sampling and incubating in laboratory almost 13,000 field collected samples, or over 380,000 fruits. For each host-fly-country association, quantitative data are presented on the weight and number of fruits collected, the proportion of infested samples, the number of adult flies emerged per kg of fruits and, whenever available, the percentage of individual fruits infested. All the published records of each fly-host-country association are cited and erroneous or dubious published records are rectified or commented. Laboratory forced infestation data are also cited and reviewed