BIOMAT Database Logo BIOMAT Database Logo

Induction of PreB cell apoptosis by 7,12-dimethylbenz[a]anthracene in long-term primary murine bone marrow cultures. 1997

K Yamaguchi, and R A Matulka, and A M Shneider, and P Toselli, and A F Trombino, and S Yang, and L J Hafer, and K K Mann, and X J Tao, and J L Tilly, and R I Near, and D H Sherr
Department of Environmental Health, Boston University Schools of Medicine and Public Health, Massachusetts, USA.

Numerous studies demonstrate that polycyclic aromatic hydrocarbons (PAH) suppress immunity by modifying the function of both B and T cells. Relatively few studies have assessed the effects of these common environmental chemicals on immature lymphocytes. In the present study, long-term primary bone marrow cultures were employed to investigate the effects of a prototypic PAH and aryl hydrocarbon receptor (AhR) agonist, 7,12-dimethylbenz[a]anthracene (DMBA), on immature B lymphocytes. In this system, immature preB cells are maintained in a supportive microenvironment provided by bone marrow stromal cells. Results presented here demonstrate that (1) exposure of primary bone marrow cultures to DMBA results in preB cell death by apoptosis; (2) notably low doses of DMBA (> or = 10(-8) M) induce preB cell apoptosis; (3) in long-term cultures, bone marrow stromal cells, but not preB cells, express AhR mRNA and protein as determined by in situ hybridization, RT-PCR, and immunoblotting; (4) freshly isolated unfractionated bone marrow cells, but not purified bone marrow B cells, express AhR protein as assessed by immunohistochemistry; (5) alpha-naphthoflavone, a competitive AhR inhibitor and cytochrome P450 antagonist, completely blocks DMBA-induced preB cell apoptosis in primary bone marrow cultures; and (6) DMBA or benzo[a]pyrene injection in vivo results in bone marrow cell apoptosis consistent with the death of hematopoietic cells clustered around stromal elements. The results implicate programmed cell death as a mechanism underlying DMBA-mediated immunosuppression and suggest that preB cell death is influenced by local interactions with AhR+ bone marrow stromal cells.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006412 Hematopoietic Stem Cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001402 B-Lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D015127 9,10-Dimethyl-1,2-benzanthracene Polycyclic aromatic hydrocarbon found in tobacco smoke that is a potent carcinogen. 7,12-Dimethylbenzanthracene,7,12-Dimethylbenz(a)anthracene,7,12 Dimethylbenzanthracene
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018336 Receptors, Aryl Hydrocarbon Cytoplasmic proteins that bind certain aryl hydrocarbons, translocate to the nucleus, and activate transcription of particular DNA segments. AH receptors are identified by their high-affinity binding to several carcinogenic or teratogenic environmental chemicals including polycyclic aromatic hydrocarbons found in cigarette smoke and smog, heterocyclic amines found in cooked foods, and halogenated hydrocarbons including dioxins and polychlorinated biphenyls. No endogenous ligand has been identified, but an unknown natural messenger with a role in cell differentiation and development is suspected. AH Receptors,Aryl Hydrocarbon Receptors,Dioxin Receptors,Receptors, AH,Receptors, Dioxin,TCDD Receptors,AH Receptor,Aryl Hydrocarbon Receptor,Dioxin Receptor,Polyaromatic Hydrocarbon Receptor,Polyaromatic Hydrocarbon Receptors,Receptors, 2,3,7,8-Tetrachlorodibenzo-p-dioxin,Receptors, Polyaromatic Hydrocarbon,Receptors, TCDD,TCDD Receptor,Receptor, AH,Receptor, Aryl Hydrocarbon,Receptor, Dioxin,Receptor, Polyaromatic Hydrocarbon,Receptor, TCDD

Related Publications

K Yamaguchi, and R A Matulka, and A M Shneider, and P Toselli, and A F Trombino, and S Yang, and L J Hafer, and K K Mann, and X J Tao, and J L Tilly, and R I Near, and D H Sherr
The metabolism of 7,12-dimethylbenz(a)anthracene in cell cultures.
November 1968, International journal of cancer,
K Yamaguchi, and R A Matulka, and A M Shneider, and P Toselli, and A F Trombino, and S Yang, and L J Hafer, and K K Mann, and X J Tao, and J L Tilly, and R I Near, and D H Sherr
Bone marrow stromal cell cytochrome P4501B1 is required for pre-B cell apoptosis induced by 7,12-dimethylbenz[a]anthracene.
December 1999, Molecular pharmacology,
K Yamaguchi, and R A Matulka, and A M Shneider, and P Toselli, and A F Trombino, and S Yang, and L J Hafer, and K K Mann, and X J Tao, and J L Tilly, and R I Near, and D H Sherr
Role of bone marrow in induction of thymic lymphomas by neonatal injection of 7,12-dimethylbenz[a]anthracene.
August 1968, Journal of the National Cancer Institute,
K Yamaguchi, and R A Matulka, and A M Shneider, and P Toselli, and A F Trombino, and S Yang, and L J Hafer, and K K Mann, and X J Tao, and J L Tilly, and R I Near, and D H Sherr
The metabolism in vitro of 7,12-dimethylbenz[a]-anthracene by human bone marrow.
July 1987, Cancer letters,
K Yamaguchi, and R A Matulka, and A M Shneider, and P Toselli, and A F Trombino, and S Yang, and L J Hafer, and K K Mann, and X J Tao, and J L Tilly, and R I Near, and D H Sherr
Formation of glucuronic acid conjugates of 7,12-dimethylbenz(a)anthracene phenols in 7,12-dimethylbenz(a)anthracene-treated hamster embryo cell cultures.
October 1978, Cancer research,
K Yamaguchi, and R A Matulka, and A M Shneider, and P Toselli, and A F Trombino, and S Yang, and L J Hafer, and K K Mann, and X J Tao, and J L Tilly, and R I Near, and D H Sherr
Chromosome aberrations induced in rat bone marrow cells by 7,12-dimethylbenz[a]-anthracene.
September 1969, Journal of the National Cancer Institute,
K Yamaguchi, and R A Matulka, and A M Shneider, and P Toselli, and A F Trombino, and S Yang, and L J Hafer, and K K Mann, and X J Tao, and J L Tilly, and R I Near, and D H Sherr
7,12-Dimethylbenz[a]anthracene-induced bone marrow toxicity is p53-dependent.
July 2003, Toxicological sciences : an official journal of the Society of Toxicology,
K Yamaguchi, and R A Matulka, and A M Shneider, and P Toselli, and A F Trombino, and S Yang, and L J Hafer, and K K Mann, and X J Tao, and J L Tilly, and R I Near, and D H Sherr
Function of bone marrow in suppressing thymic lymphomas induced by 7,12-dimethylbenz(a)anthracene.
February 1973, Journal of the National Cancer Institute,
K Yamaguchi, and R A Matulka, and A M Shneider, and P Toselli, and A F Trombino, and S Yang, and L J Hafer, and K K Mann, and X J Tao, and J L Tilly, and R I Near, and D H Sherr
Preleukemic proliferative changes in murine bone marrow after single and multiple 7,12-dimethylbenz(a)anthracene (DMBA)-applications.
January 1993, Leukemia research,
K Yamaguchi, and R A Matulka, and A M Shneider, and P Toselli, and A F Trombino, and S Yang, and L J Hafer, and K K Mann, and X J Tao, and J L Tilly, and R I Near, and D H Sherr
Proximal events in 7,12-dimethylbenz[a]anthracene-induced, stromal cell-dependent bone marrow B cell apoptosis: stromal cell-B cell communication and apoptosis signaling.
September 2010, Journal of immunology (Baltimore, Md. : 1950),
Copied contents to your clipboard!