The Molecular Dosimetry of DNA Adducts Formed by Continuous Exposure of Rats to Alkylating Hepatocarcinogens

2015 ◽  
pp. 42-51 ◽  
Author(s):  
J. A. Swenberg ◽  
F. C. Richardson ◽  
L. Tyeryar ◽  
F. Deal ◽  
J. Boucheron
Keyword(s):  
Dna Adducts ◽  
Continuous Exposure

Sustained Overexpression of CYP1A1 and 1B1 and Steady Accumulation of DNA Adducts by Low-Dose, Continuous Exposure to Benzo[a]pyrene by Polymeric Implants

2011 ◽  
Vol 24 (11) ◽  
pp. 1937-1943 ◽  
Author(s):  
Jeyaprakash Jeyabalan ◽  
Manicka V. Vadhanam ◽  
Srivani Ravoori ◽  
Ramesh C. Gupta
Keyword(s):  
Dna Adducts ◽  
Low Dose ◽  
Continuous Exposure ◽  
Polymeric Implants

Toxic effects of inhaled DMMP on the kidneys of Fischer-344 rats

1987 ◽  
Vol 45 ◽  
pp. 880-881
Author(s):  
D.R. Mattie ◽  
C.J. Hixson
Keyword(s):  
Left Kidney ◽  
Inhalation Exposure ◽  
Electron Microscopic Examination ◽  
Exposure Period ◽  
Male Rats ◽  
Continuous Exposure ◽  
Fischer 344 Rats ◽  
Electron Microscopic ◽  
Thin Sections ◽  
Fischer 344

Dimethylmethylphosphonate (DMMP) is a simple organophosphate used industrially as a flame retardant and to lower viscosity in polyester and epoxy resins. The military considered the use of DMMP as a nerve gas simulant. Since military use of DMMP involved exposure by inhalation, there was a need for a subchronic inhalation exposure to DMMP to fully investigate its toxic potential.Male Fischer-344 rats were exposed to 25 ppm or 250 ppm DMMP vapor on a continuous basis for 90 days. An equal number of control rats were sham-exposed. Following the 90-day continuous exposure period, 15 male rats were sacrificed from each group. Two rats from each group had the left kidney perfused for electron microscopic examination. The kidneys were perfused from a height of 150 cm water with 1% glutaraldehyde in Sorensen's 0.1M phosphate buffer pH 7.2. An additional kidney was taken from a rat in each group and fixed by immersion in 2.5% glutaraldehyde and 2% paraformaldehyde in 0.1M cacodylate buffer pH 7.4. A portion of the 9 kidneys collected for electron microscopy were processed into Epon 812. Thin sections, stained with uranyl acetate and lead citrate, were examined with a JEOL 100B Transmission Electron Microscope. Microvilli height was measured on photographs of the cells of proximal tubules. This data, along with morphologic features of the cells, allows the proximal convoluted tubules (PCT) to be identified as being S1, S2, or S3 segment PCT.

Cytochrome P4502E1 is responsible for miscoding etheno-Dna adducts induced by ethanol in the liver

2008 ◽  
Vol 46 (01) ◽  
Author(s):  
Y Wang ◽  
J Nair ◽  
S Mueller ◽  
F Stickel ◽  
H Bartsch ◽  
...  
Keyword(s):  
Dna Adducts ◽  
Cytochrome P4502e1

Long-Term Copper Toxicity on Scenedesmus quadricauda and Complexing Polypeptides

1995 ◽  
Vol 30 (2) ◽  
pp. 265-276 ◽  
Author(s):  
Denis Bussières ◽  
Raynald Côté ◽  
Clément Richard ◽  
Édith St-Pierre
Keyword(s):  
Heavy Metal ◽  
Sharp Increase ◽  
Copper Ions ◽  
Copper Toxicity ◽  
Scenedesmus Quadricauda ◽  
Continuous Exposure ◽  
Exponential Curve ◽  
Negative Exponential

Abstract Long-term copper toxicity has been demonstrated in Scenedesmus quadricauda. Upon continuous exposure to copper ions at 250 μg/L, the algae responded by a sharp increase in the synthesis of complexing polypeptides to chelate Cu. Complexing polypeptides gradually decreased, as observed by six sampling tests over 732 h, resembling to a negative exponential curve. This gradual diminution is considered to be a prime mechanism of acclimation or of adaptation to a heavy metal contaminated environment.

scholarly journals Identification of New Markers of Alcohol-Derived DNA Damage in Humans

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 366
Author(s):  
Valeria Guidolin ◽  
Erik S. Carlson ◽  
Andrea Carrà ◽  
Peter W. Villalta ◽  
Laura A. Maertens ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Adducts ◽  
Neutral Loss ◽  
Alcohol Exposure ◽  
Dose Dependence ◽  
Accurate Mass ◽  
Constant Neutral Loss ◽  
Covalent Modifications ◽  
Underlying Mechanisms

Alcohol consumption is a risk factor for the development of several cancers, including those of the head and neck and the esophagus. The underlying mechanisms of alcohol-induced carcinogenesis remain unclear; however, at these sites, alcohol-derived acetaldehyde seems to play a major role. By reacting with DNA, acetaldehyde generates covalent modifications (adducts) that can lead to mutations. Previous studies have shown a dose dependence between levels of a major acetaldehyde-derived DNA adduct and alcohol exposure in oral-cell DNA. The goal of this study was to optimize a mass spectrometry (MS)-based DNA adductomic approach to screen for all acetaldehyde-derived DNA adducts to more comprehensively characterize the genotoxic effects of acetaldehyde in humans. A high-resolution/-accurate-mass data-dependent constant-neutral-loss-MS3 methodology was developed to profile acetaldehyde-DNA adducts in purified DNA. This resulted in the identification of 22 DNA adducts. In addition to the expected N2-ethyldeoxyguanosine (after NaBH3CN reduction), two previously unreported adducts showed prominent signals in the mass spectra. MSn fragmentation spectra and accurate mass were used to hypothesize the structure of the two new adducts, which were then identified as N6-ethyldeoxyadenosine and N4-ethyldeoxycytidine by comparison with synthesized standards. These adducts were quantified in DNA isolated from oral cells collected from volunteers exposed to alcohol, revealing a significant increase after the exposure. In addition, 17 of the adducts identified in vitro were detected in these samples confirming our ability to more comprehensively characterize the DNA damage deriving from alcohol exposures.

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