Toxicological Sciences, Vol 49, 124-132, Copyright © 1999 by Society of Toxicology
JG Lewis, DG Graham, WM Valentine, RW Morris, DL Morgan and RC Sills
Even though atherosclerotic cardiovascular disease (ACVD) is the number one
cause of death in the United States, the effects of environmental toxicants
on this process are less well studied than the effects of chemicals on the
second leading cause of death, cancer. There is considerable
epidemiological evidence that workers exposed to carbon disulfide (CS2)
have increased rates of ACVD, and there is conflicting evidence of the
atherogenic potential of CS2 from animal studies. Chemical modification,
such as oxidation of low-density lipoproteins (LDL), is tightly associated
with increased LDL uptake by macrophages and the development of arterial
fatty streaks. CS2 has been previously demonstrated to modify several
proteins in vitro including LDL, and others in vivo through derivatization
and covalent cross-linking. To investigate both the capacity of CS2 to
induce arterial fatty deposits by itself, and its ability to enhance the
rate of fatty deposit formation induced by a western style, high fat diet,
groups of 20 female C57BL/6 mice were exposed to 0, 50, 500, or 800 ppm CS2
by inhalation. Half the animals in each group were placed on an atherogenic
high fat diet and half on a control diet (NIH-07). Animals were sacrificed
after 1, 4, 8, 12, 16, or 20 weeks of exposure, and the rates of fatty
deposit formation under the aortic valve leaflets were evaluated. Exposure
of mice on the control diet to 500 and 800 ppm CS2 induced a small but
significant increase in the rate of fatty deposit formation over
non-exposed controls. A more striking result was observed in the animals on
the high fat diet. There was marked enhancement of the rate of fatty
deposit formation in mice exposed to 500 and 800 ppm over the animals on
the high fat diet alone. In addition, there was a small but significant
enhancement in mice exposed to 50 ppm over the rate of fatty deposit
formation induced by the high fat diet alone. Analysis of erythrocyte
spectrin for protein cross- linking revealed a dose-dependent formation of
alpha- and beta- heterodimers in animals on both diets. These data
demonstrate that CS2 is atherogenic at high concentrations, but more
importantly, suggest that, in conjunction with other risk factors, CS2 at
relatively low concentrations can enhance atherogenesis.
ARTICLES
Exposure of C57BL/6 mice to carbon disulfide induces early lesions of atherosclerosis and enhances arterial fatty deposits induced by a high fat diet
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA. lewis026@mc.duke.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y Nishiwaki, T Takebayashi, T O'Uchi, T Nomiyama, T Uemura, H Sakurai, and K Omae Six year observational cohort study of the effect of carbon disulphide on brain MRI in rayon manufacturing workers Occup. Environ. Med., March 1, 2004; 61(3): 225 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T Takebayashi, Y Nishiwaki, T Uemura, H Nakashima, T Nomiyama, H Sakurai, and K Omae A six year follow up study of the subclinical effects of carbon disulphide exposure on the cardiovascular system Occup. Environ. Med., February 1, 2004; 61(2): 127 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.C. Sills, W.M. Valentine, V. Moser, D.G. Graham, and D.L. Morgan Characterization of Carbon Disulfide Neurotoxicity in C57BL6 Mice: Behavioral, Morphologic, and Molecular Effects Toxicol Pathol, January 1, 2000; 28(1): 142 - 148. [Abstract] [PDF]
|
|