Uptake, distribution, and formation of hemoglobin and DNA adducts after inhalation of C2-C8 1-alkenes (olefins) in the rat

Abstract

Absorption, distribution, elimination and hemoglobin and DNA adduct formation were studied in the rat after inhalation of individual C2-C8 1-alkenes (olefins) at 300 p.p.m., 12 h a day for 3 consecutive days. The concentrations of olefins were measured in blood, lung, brain, liver, kidney and perirenal fat immediately after each exposure and 12 h after the third exposure. DNA adducts were determined by 32P-postlabeling in liver, and lymphocytes sampled immediately after the last exposure. Hemoglobin adducts were determined by GC/MS and GC/MS/MS in erythrocytes sampled immediately after the last exposure. Concentrations of 1-alkenes in blood and organs reached a steady-state level after the first 12 h exposure, and the concentrations 12 h after the last exposure were generally low, except in fat tissue. Concentrations of 1-alkenes in blood and the different tissues increased with increasing number of carbon atoms. In contrast, levels of hemoglobin and DNA adducts decreased with increasing number of carbon atoms. The decrease was most pronounced from C2 to C3. The decrease through the whole homologous series from ethene to 1-octene was most pronounced for hemoglobin adducts followed by the DNA adducts in the lymphocytes. All 1-alkenes caused formation of detectable levels of hemoglobin and DNA adducts, although the levels of hemoglobin adducts after C4-C8 exposure were low. The project illustrates important aspects of the use of biomarkers. The structure-activity approach gives possibilities for extrapolation within the homologous series.

Simultaneous quantification of haemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile, acrylamide and glycidamide in human blood by isotope-dilution GC/NCI-MS/MS

“…In addition, multiple (animal) studies could show a close relationship between the binding of several carcinogenic substances (e.g. ethylene oxide, propylene oxide, alkenes, glycidamide) to haemoglobin and DNA in various tissues [1][2][3][4][5]. A human study could even show a close relationship between haemoglobin adducts and DNA-adducts in white blood cells of workers with occupational exposure to propylene oxide [6].…”

Ethylene Oxide in Blood of Ethylene-Exposed B6C3F1 Mice, Fischer 344 Rats, and Humans

“…Backgrounds were not taken into consideration. HEG levels were calculated for lymphocyte DNA. c Walker et al (2000; DNA adducts are means of the levels measured in liver, spleen, brain, and lung). d Wu et al (1999; Means of DNA adducts measured in liver, spleen, brain, and lung). e Rusyn et al (2005). f Eide et al (1995; DNA adducts are means of the levels measured in lymphocytes and liver). g Zhao et al (1997; 20 days after exposure, the difference between adduct level after exposure and background was zero). …”

“…: 75-21-8), as has been demonstrated directly in vivo in rats (Fennell et al , 2004; Filser and Bolt, 1984; Maples and Dahl, 1993) and in vitro in liver microsomes of rats (Li et al , 2011a; Schmiedel et al , 1983), mice, and humans (Li et al , 2011a). In these species when exposed to ET, the formation of EO-characteristic hydroxyethyl adducts to hemoglobin and/or DNA was shown (mice: Ehrenberg et al , 1977; Segerbäck, 1983; Walker et al , 2000; Wu et al , 1999; rats: Eide et al , 1995; Rusyn et al , 2005; Walker et al , 2000; Wu et al , 1999; humans: Filser et al , 1992; Kautiainen and Törnqvist, 1991; Törnqvist et al , 1989). EO is a direct protein- and DNA-alkylating agent, is mutagenic in prokaryotic and eukaryotic—including mammalian—cells, and carcinogenic in mice and rats (reviewed in IARC, 1994b, 2008, 2012).…”

DNA Adducts and Mutations in Occupational and Environmental Biomonitoring

“…However, the decrease was 5-fold in liver, 30- Figure 1. Liver and lymphocyte DNA (adducts/107 normal nucleotides) and hemoglobin N-(2-hydroxy)valine adducts (x 500 pmol/g) of rats exposed to 300 ppm of alkenes from ethene (C2) to octene (C8) for 12 hr on 3 consecutive days (8). DNA react., reactivity of alkene epoxides with DNA in vitro; Hb, hemoglobin.…”