Quantitative changes in sets of proteins as markers of biological response

Conference · Mon Jan 01 04:00:00 EST 1990

OSTI ID:6287343

Giometti, C S; Taylor, J; Gemmell, M A; Tollaksen, S L ^[1]; Lalwani, N D; Reddy, J K ^[2]

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1. Argonne National Lab., IL (USA)
2. Northwestern Univ., Chicago, IL (USA)

Exposure to either physical or chemical insults triggers a cascade of bio-chemical events within the target cell. This response requires adjustment within the protein population of the cell, some proteins becoming more abundant (those involved in the cellular response), others less abundant (those not required or counterproductive to the response). Thus, quantitative changes in the global protein population of an exposed biological system may well serve as an indicator of exposure, provided the alterations observed are selective and dose-dependent. In this paper we present results from a study in which liver protein changes induced by exposure of mice to chemicals known to cause peroxisome proliferation and subsequent hepatocellular carcinoma where monitored. Clofibrate, and its chemical analog ciprofibrate, are hypolipidemic drugs. Di-(ethylhexyl)phthalate (DEHP) is a plasticizer used widely in disposable containers for blood products. WY-14643 is a chemical shown to cause hypolipidemic and peroxisome proliferation, similar to clofibrate, ciprofibrate and DEHP, but structurally different from these three chemicals. Thus, two of the four chemicals are structurally similar while the remaining two are very distinct, although all four chemicals cause the same gross biological response. Our results show that although common protein effects are observed in mice exposed to these chemicals, each chemical also causes specific alterations in selective subsets of proteins that could serve as markers of a particular exposure. 13 refs., 4 figs., 1 tab.

• Research Organization: Argonne National Lab., IL (USA)
• Sponsoring Organization: DOE/ER
• DOE Contract Number: W-31109-ENG-38
• OSTI ID: 6287343
• Report Number(s): CONF-9010249-2; ON: DE91006368
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL INDICATORS
CARBOXYLIC ACID SALTS
CARCINOMAS
DISEASES
DOSE-RESPONSE RELATIONSHIPS
ELECTROPHORESIS
LIVER CELLS
MAMMALS
MATERIALS
MICE
NEOPLASMS
ORGANIC COMPOUNDS
PHTHALATES
PLASTICIZERS
PROTEINS
RODENTS
SOMATIC CELLS
TOXIC MATERIALS
TOXICITY
TWO-DIMENSIONAL ELECTROPHORESIS
VERTEBRATES