Selective Myelotoxicity of Propanil

BLYLER, GABRIELLA; Landreth, Kenneth S.; Lillis, Terence O.; Schafer, Rosana; Theus, Sue A.; Gandy, Joan; Barnett, John B.

doi:10.1006/faat.1994.1057

Cited by 24 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two studies have demonstrated DCPA's myelotoxicity (Blyler et al, 1994;Malerba et al, 2002). Following exposure to 200 mg/kg DCPA, myeloid stem cells were reduced as analyzed using ex vivo colony-forming assays from bone marrow of acutely exposed C57Bl/6 mice (Blyler et al, 1994). Effects on early erythroid stem cells observed following in vitro exposure of human umbilical cord to DCPA supported the earlier report of myelotoxicity (Malerba et al, 2002).…”

Section: Literature Review IIsupporting

confidence: 64%

“…DCPA has been extensively described as an immunotoxicant on both primary and secondary immune organs. Two studies have demonstrated DCPA's myelotoxicity (Blyler et al, 1994;Malerba et al, 2002). Following exposure to 200 mg/kg DCPA, myeloid stem cells were reduced as analyzed using ex vivo colony-forming assays from bone marrow of acutely exposed C57Bl/6 mice (Blyler et al, 1994).…”

Section: Literature Review IImentioning

confidence: 99%

See 1 more Smart Citation

Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/beta-catenin signaling in the thymus resulting in immunomodulatory effects

Hanson¹

View full text Add to dashboard Cite

Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/β-catenin signaling in the thymus resulting in immunomodulatory effects Miranda Leah Hanson Cadmium (Cd) is both an environmental pollutant as well as a component of cigarette smoke. Recent data suggests increased cancer risks and increased mortality in environmentally exposed populations. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports in the literature of immunomodulatory effects of prenatal exposure to Cd. The sonic hedgehog (Shh) and Wnt/β−catenin pathways are required for thymocyte maturation. Several studies have demonstrated that Cd exposure affects these pathways in different organ systems. Our experiments were designed to investigate the effect of prenatal Cd exposure on thymocyte development, and to determine if these effects were linked to dysregulation of Shh and Wnt/β-catenin pathways. In addition, longer term effects of prenatal Cd on the immune system were investigated. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose (10 ppm) of Cd during pregnancy and effects on the thymus of the offspring were assessed on post-natal day 0 (PND0), while effects on the thymus and spleen were assessed on PND14 and 49. On PND0, thymocyte phenotype was determined by flow cytometry. A Gli:luciferase reporter cell line was used to measure Shh signaling. Transcription of target genes and translation of key components of both signaling pathways was assessed using real-time RT-PCR and western blot, respectively. On PND14 and 49, thymocyte and splenocyte phenotypes were analyzed, and cytokine production of splenic T cells was determined by ELISA. On PND0, prenatal Cd exposure increased the number of CD4 + cells and a subpopulation of double-negative cells (DN; CD4-CD8-). Shh and Wnt/β-catenin signaling were both decreased in the thymus; however, this was not due to altered Shh and Wnt protein levels. Target genes of Shh and Wnt/β-catenin were affected differentially among thymocyte subpopulations. On PND14 and 49, prenatal Cd exposure increased the number of DN thymocytes. In the spleen, prenatal Cd exposure had a cell type-, sex-specific effect on splenocyte phenotype and cytokine production. Collectively, these findings suggest that even very low exposure to Cd during gestation dysregulates two signaling pathways in the thymus resulting in altered thymocyte development, and this dysregulation can result in long term detrimental effects on the immune system of the offspring.

show abstract

Section: Literature Review IIsupporting

confidence: 64%

Section: Literature Review IImentioning

confidence: 99%

Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/beta-catenin signaling in the thymus resulting in immunomodulatory effects

Hanson¹

View full text Add to dashboard Cite

show abstract

“…Methemoglobinemia and hemolytic anemia have also been reported from animal studies with propanil exposure (Ambrose et al, 1972; Singleton and Murphy, 1973; Chow and Murphy, 1975; McMillan et al, 1990b, 1991). Propanil is an immunotoxicant in several models, reducing the production of cytokines as well as the number of CD4+CD8+ thymocytes (Barnett et al, 1992; Blyler et al, 1994; Frost et al, 2001; Malerba et al, 2002). Chloracne observed in industrial workers during propanil manufacture was originally ascribed to propanil, but subsequent studies have demonstrated that this toxicity was due to chemical contaminants (Morse and Baker, 1979; Kimbrough, 1980).…”

Section: Introductionmentioning

confidence: 99%

In vitro nephrotoxicity induced by propanil

Rankin

Racine

Sweeney

et al. 2008

Environmental Toxicology

View full text Add to dashboard Cite

Propanil is a postemergence herbicide used primarily in rice and wheat production in the United States. The reported toxicities for propanil exposure include methemoglobinemia, immunotoxicity, and nephrotoxicity. A major metabolite of propanil, 3,4-dichloroaniline (3,4-DCA), has been shown to be a nephrotoxicant in vivo and in vitro, but the nephrotoxic potential of propanil has not been examined in detail. The purpose of this study was to determine the nephrotoxic potential of propanil using an in vitro kidney model, determine whether in vitro propanil nephrotoxicity is due to metabolites arising from propanil hydrolysis, and examine mechanistic aspects of propanil nephrotoxicity in vitro. Propanil, 3,4-DCA, propionic acid (0.1–5.0 mM), or vehicle was incubated for 15–120 min with isolated renal cortical cells (IRCC; ~4 million cells/mL) obtained from untreated male Fischer 344 rats. Cytotoxicity was determined by measuring lactate dehydrogenase release from IRCC. In 120-min incubations, propanil induced cytotoxicity at concentrations >0.5 mM. At 1.0 mM, propanil induced cytotoxicity following 60- or 120-min exposure. Cytotoxicity was observed with 3,4-DCA (2.0 mM) at 60 and 120 min, while propionic acid (5.0 mM) induced cytotoxicity at 60 min. In IRCC pretreated with an antioxidant, cytochrome P450(CYP) inhibitor, flavin adenine dinucleotide monooxygenase activity modulator, or cyclooxygenase inhibitor before propanil exposure (1.0 mM; 120 min), only piperonyl butoxide (0.1 mM), a CYP inhibitor, pretreatment decreased propanil cytotoxicity. These results demonstrate that propanil is an in vitro nephrotoxicant in IRCC. Propanil nephrotoxicity is not primarily due to metabolites resulting from hydrolysis of propanil, but a metabolite resulting from propanil oxidation may contribute to propanil cytotoxicity.

show abstract

“…Bone marrow hematopoiesis can be altered by exposure to drugs and chemicals resulting in immune suppression (Blyler et al, 1994;Thurmond and Gasiewicz, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…Propanil is an amide herbicide that is used in rice and wheat production in the United States. Exposure is toxic to developing immune cells, suppressing myeloid stem cell colony formation in the bone marrow and selectively decreasing the number of progenitor T cells in the thymus (Blyler et al, 1994;Zhao et al, 1995). In addition,…”

Section: Introductionmentioning

confidence: 99%

Changes in immune cell populations and the antibody response to Streptococcus pneumoniae after exposure to a mixture of herbicides

Rosa¹

View full text Add to dashboard Cite

Patricia de la Rosa Changes in immune cell populations and the antibody response to Streptococcus pneumoniae after exposure to a mixture of herbicides ABSTRACT iii DEDICATION I would like to dedicate this dissertation to my family: to my parents, John and Mary Kosco who encouraged me and imparted in me the discipline to persevere in the face of adversity, to my children, Charlie and Lizzy de la Rosa, who believed in me and never complained, and to my sister and brother-in-law, Ellen Kosco and Ron Balvers, for their unfailing generosity and support. This work is a testimony to your love. iv ACKNOWLEDGEMENTS I would most like to thank my advisor, Rosana Schafer, who, like all great mentors, provided just the right amount of support, encouragement and unrelenting drive for perfection necessary to instill in me a love for science and professionalism. I would also like to thank Rosana for her interest in both my personal and professional growth. Her friendship made the Schafer lab a fun place to work. I am also in debt to John Barnett who opened his lab and its resources to me. Thank you for your support at the start of my graduate career, as well as every day since.

show abstract

Selective Myelotoxicity of Propanil

Cited by 24 publications

References 0 publications

Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/beta-catenin signaling in the thymus resulting in immunomodulatory effects

Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/beta-catenin signaling in the thymus resulting in immunomodulatory effects

In vitro nephrotoxicity induced by propanil

Changes in immune cell populations and the antibody response to Streptococcus pneumoniae after exposure to a mixture of herbicides

Contact Info

Product

Resources

About