Printer Friendly

Clues to a new class of liver carcinogens.

Clues to a new class of liver carcinogens

Peroxisomes are a curiosity. These round, dense constituents of plant and animal cells harbor enzymes to make and break hydrogen peroxide (H.sub.2.O.sub.2.). While it's unclear what beneficial role. If any, peroxisomes play in mammalian cells, new research suggests they can become the means by which one class of chemicals triggers the development of apparently novel liver cancers.

A number of potentially important chemicals -- including several powerful cholesterol-lowering drugs, herbicides and plasticizers -- are liver carcinogens that uniformly elude detection by short-term carcinogen-screening assays, such as the Ames test. The reason, explains toxicologist Janardan Reddy at Northwestern University Medical School in Chicago, is that the short-term screening tests look for chemicals that cause genetic mutations in bacteria. But the liver carcinogens he studies don't interact directly with DNA. Instead, they trigger the liver to produce peroxisomes -- 15 to 20 times the normal number.

These peroxisome-proliferating chemicals (PPCs) also activate a trio of genes inside liver-cell nuclei. Within minutes to hours of PPC exposure, the genetic trio stimulates a cell's peroxisome production of H.sub.2.O.sub.2.--to levels 30 or 40 times normal. Meanwhile, a peroxisome's H.sub.2.O.sub.2.-degrading enzymes will not even double.

Elevated peroxisome-H.sub.2.O.sub.2 concentrations, caused by this mismatch between its production and breakdown rates, eventually result in large quantities of the potentially toxic chemical diffusing into liver cells. There it reacts with metals, such as iron and copper, forming toxic "free radicals" -- highly reactive molecular fragments, such as hydroxyl (OH). "We feel that the hydroxyl radical produced by H.sub.2.O.sub.2 over time causes the DNA damage or whatever is needed to induce a cancer," Reddy says.

In the January TOXICOLOGY AND APPLIED PHARMACOLOGY, Reddy and his co-workers report data indicating that the liver is the sole target of PPC toxicity and suggesting that PPC-induced cancers form quite differently from other liver cancers. Two proteins that serve as markers of classical liver tumors -- gamma-glutamyltranspeptidase and glutathione S-transferase-P--are conspicuously absent in PPC-induced tumors. Reddy says this suggests the PPC free-radical process may trigger a new cancer-causing gene.

It also suggests, he says, that chemicals appearing benign in short-term carcinogen screening tests should be subjected to two-week peroxisome-proliferation assays in animals before further commercial development goes ahead. Although not required to do so, a few U.S. companies have begun subjecting suspect chemicals to such tests.

Preliminary data indicate rats and mice are much more sensitive to PPCs than are humans. If tissue-culture studies prove useful in identifying exposures below which no peroxisome proliferation occurs -- "we may be able to determine the risk of these useful chemicals" and design nontoxic exposures to them, Reddy says.
COPYRIGHT 1989 Science Service, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 1989, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

Article Details
Printer friendly Cite/link Email Feedback
Author:Raloff, Janet
Publication:Science News
Date:Feb 25, 1989
Words:461
Previous Article:Ozone violators increase.
Next Article:The diagnostic dilemma: is revising the official manual of mental disorders a prescription for confusion?
Topics:


Related Articles
Cells haywire in electromagnetic field?
Carcinogens au naturel?
Cell videos catch asbestos in the act.
Tomoxifen's maker publishes cancer data.
Not so hot hot dogs? Fleshing out risks associated with how we treat meat.
Coffee: key to cooked-meat vulnerability?
Reducing carcinogens in public schools: a non-regulatory approach by a regulatory agency.
U.N. body rules tamoxifen a carcinogen.
Evaluating dietary carcinogens.
Nonsmokers inhale carcinogen.

Terms of use | Copyright © 2017 Farlex, Inc. | Feedback | For webmasters