The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 1983-1984

Studies Using Hepatocyte Culture to Investigate the Mechanism of Hepatotoxicity of Chemicals that Cause Peroxisome Proliferation

Timothy J.B. Gray, PhD
British Industrial Biological Research Association, Carshalton, England

Problem

An increasing number of structurally unrelated chemicals is known to cause proliferation of liver cell peroxisomes (cell organelles which contain enzymes that produce hydrogen peroxide). There is circumstantial evidence that this response is causally related to chronic hepatotoxicity.

Little is known about the biochemical consequences of peroxisome proliferation, and the toxicological significance of this remains uncertain.

Increased production of hydrogen peroxide or depletion of cellular defenses against reactive oxygen intermediates may initiate cell injury.

Impact of the Research

The study will use liver cell cultures from various species, which are highly responsive to peroxisome proliferation in vitro. The research should determine whether cell culture can reflect known species differences in response in vitro and whether liver cells could be used to predict the susceptibility of human liver to peroxisome proliferation.