IL-2Rα KO mice exhibit maternal microchimerism and reveal nuclear localization of IL-2Rα in lymphoid and non-lymphoid cells.

Introduction: IL-2Rα knock out (KO) mice have been instrumental to discovering the immunoregulatory properties of IL-2Rα. While initially thought of only as a stimulatory cytokine, IL-2 and IL-2Rα KO mice revealed that this cytokine-receptor system controls immune responses through restimulation-induced cell death and by promoting the survival of T regulatory cells. Although described mostly in the context of lymphocytes, recent studies by our laboratory showed that IL-2R is expressed in smooth muscle cells.

IL-2RαKO mice exhibit maternal microchimerism and reveal nuclear localization of IL-2Rα in lymphoid and non-lymphoid cells.

IL-2Rα KO mice have been instrumental to discovering the immunoregulatory properties of IL-2Rα. While initially thought of only as a stimulatory cytokine, IL-2 and IL-2Rα knock out (KO) mice revealed that this cytokine-receptor system controls immune responses through restimulation-induced cell death and by promoting the survival of T regulatory cells. Although described mostly in the context of lymphocytes, recent studies by our laboratory showed that IL-2R is expressed in smooth muscle cells.

Nasal uptake of inhaled acrolein in rats.

An improved understanding of the relationship between inspired concentration of the potent nasal toxicant acrolein and delivered dose is needed to support quantitative risk assessments. The uptake efficiency (UE) of 0.6, 1.

Exposure of hematopoietic stem cells to benzene or 1,4-benzoquinone induces gender-specific gene expression.

Chronic exposure to benzene results in progressive decline of hematopoietic function and may lead to the onset of various disorders, including aplastic anemia, myelodysplastic syndrome, and leukemia. Damage to macromolecules resulting from benzene metabolites and misrepair of DNA lesions may lead to changes in hematopoietic stem cells (HSCs) that give rise to leukemic clones. We have shown previously that male mice exposed to benzene by inhalation were significantly more susceptible to benzene-induced toxicities than females.

Gene expression profile in bone marrow and hematopoietic stem cells in mice exposed to inhaled benzene.

Acute myeloid leukemia and chronic lymphocytic leukemia are associated with benzene exposure. In mice, benzene induces chromosomal breaks as a primary mode of genotoxicity in the bone marrow (BM). Benzene-induced DNA lesions can lead to changes in hematopoietic stem cells (HSC) that give rise to leukemic clones.

Variations in Prkdc and susceptibility to benzene-induced toxicity in mice.

Benzene, a carcinogen that induces chromosomal breaks, is strongly associated with leukemias in humans. Possible genetic determinants of benzene susceptibility include proteins involved in repair of benzene-induced DNA damage. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), encoded by Prkdc, is one such protein.

Male mice deficient in microsomal epoxide hydrolase are not susceptible to benzene-induced toxicity.

Enzymes involved in benzene metabolism are likely genetic determinants of benzene-induced toxicity. Polymorphisms in human microsomal epoxide hydrolase (mEH) are associated with an increased risk of developing leukemia, specifically those associated with benzene. This study was designed to investigate the importance of mEH in benzene-induced toxicity.

Induction of micronuclei in wild-type and p53(+/-) transgenic mice by inhaled bromodichloromethane.

Bromodichloromethane (BDCM) is commonly present in trace amounts in drinking water as a disinfection by-product. BDCM has been shown to be carcinogenic in mice and rats when given by gavage at relatively high doses. Genotoxic activity as well as induced regenerative cell proliferation may contribute to the carcinogenic potential of BDCM.

p53 heterozygosity alters the mRNA expression of p53 target genes in the bone marrow in response to inhaled benzene.

C57BL/6 Trp53 heterozygous (N5) mice (p53+/- mice) show an increased sensitivity to tumorigenesis following exposure to genotoxic compounds and are being used as an alternate animal model for carcinogenicity testing. However, there is relatively little data regarding the effect of p53 heterozygosity on the genomic and cellular responses of target tissues in these mice to toxic insult, especially under chronic exposure conditions used in carcinogenicity bioassays. We hypothesized that heterozygosity at the p53 locus in p53+/- mice alters the expression of bone marrow p53-regulated genes involved in cell cycle control and apoptosis during chronic genotoxic stress.