Biomaterial Database

Apoptosis is the mode of cell death caused by carcinogenic chromium. 1994

L J Blankenship, and F C Manning, and J M Orenstein, and S R Patierno

Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.

The role of apoptosis in the mechanism of toxicity of hexavalent chromium, a human carcinogen, was investigated. Chinese hamster ovary (CHO) cells were treated with 150 or 300 microM sodium chromate for 2 hr, doses which decreased colony-forming efficiency to 53 and 5% of control, respectively. Cell growth was inhibited at least up to Day 8 after treatment. DNA synthesis was inhibited to 30 and 19% of control at 1 hr after treatment, and did not begin to recover until Day 4 after treatment. Protein synthesis was inhibited by 52 and 60% in 150 and 300 microM treated cells, respectively, 1 h after treatment, and recovered to 142 and 93%, respectively, at 24 hr. Incubation of cells with nontoxic doses of cycloheximide for 24 hr after treatment produced synergistic toxicity with chromate in colony-forming efficiency assays. Ion gradients persisted to Day 2 as revealed by exclusion of trypan blue dye in 97% of treated cells. Fluorescence microscopy of acridine orange-stained cells revealed morphological features of apoptosis including nuclear fragmentation in more than 90% of detached nonadherent cells and up to 22% of adherent cells by Day 2 after treatment. Untreated cells remained morphologically normal. Transmission electron microscopy of chromate treated cells showed characteristic features of apoptosis including chromatin margination and fragmentation, and cytoplasmic condensation with intact membrane and organelle structure. Internucleosomal DNA fragmentation (IDF) was delayed for at least 24 hr, whereafter it was detected in both adherent and nonadherent cells through Day 5 after treatment. These results indicate apoptosis as the mode of cell death caused by chromium and imply that apoptosis must be considered as a component of chromium-induced multistage carcinogenesis.

UI	MeSH Term	Description	Entries
D008854	Microscopy, Electron	Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.	Electron Microscopy
D008856	Microscopy, Fluorescence	Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.	Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D011500	Protein Synthesis Inhibitors	Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.	Protein Synthesis Antagonist,Protein Synthesis Antagonists,Protein Synthesis Inhibitor,Antagonist, Protein Synthesis,Antagonists, Protein Synthesis,Inhibitor, Protein Synthesis,Inhibitors, Protein Synthesis,Synthesis Antagonist, Protein,Synthesis Inhibitor, Protein
D002273	Carcinogens	Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.	Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002840	Chromates	Salts of chromic acid containing the CrO(2-)4 radical.	Chromate
D003114	Colony-Forming Units Assay	A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.	Clonogenic Cell Assay,Stem Cell Assay,Clonogenic Cell Assays,Colony Forming Units Assays,Colony-Forming Units Assays,Stem Cell Assays,Assay, Clonogenic Cell,Assay, Colony-Forming Units,Assay, Stem Cell,Assays, Clonogenic Cell,Assays, Colony-Forming Units,Assays, Stem Cell,Colony Forming Units Assay
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D006224	Cricetinae	A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.	Cricetus,Hamsters,Hamster
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