Lack of Toluene-Induced Dominant Lethals in Rats

Author Institution: Department of Biology, Central State UniversityThe mutagenic potential of toluene was investigated with the dominant lethal mutation assay. Male Sprague Dawley rats (8-10 wk old) were injected intraperitoneally for 5 consecutive days with 346 and 692 mg per kg body weight of toluene in corn oil. To analyze for the effect of toluene on several germ cell stages, each male was mated with one untreated, virgin female per week for up to 7 weeks. Females were sacrificed 14 to 17 d after insemination for analysis of their uterine contents. The total number of implantations and the number of dead and living embryos per pregnant female were determined. From these data the dominant lethal mutation index was calculated. There was no significant effect of toluene on the number of implantations (total, dead, or alive) per pregnant female per week. The different stages of spermatogenesis from late primary spermatocyte to fully mature sperm were not affected by the action of toluene as measured by the dominant lethal mutation assay. The dominant lethal mutation indices were small positive and negative percentages, suggesting that toluene did not induce dominant lethal mutations in the germ cells of male Sprague Dawley rats under the conditions tested

Biomarkers of NAFLD progression: a lipidomics approach to an epidemic 1 [S]

The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an "omics" approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD

Biomarkers of NAFLD progression: a lipidomics approach to an epidemic

The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an “omics” approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD