Expression of Glycosidase Activity in Livers of Male F-344 Rats Given
Dietary Phthalates After Initiation or in the Two Stage Initiation/Promotion
Model
J.H. Carter*, H.W. Carter*, A.B. DeAngelo**. and F.B. Daniel** *Wood Hudson
Cancer Research Laboratory, 931 Isabella St., Newport, KY 41071, and **United
States Environmental Protection Agency, Cincinnati, OH 45268
INTRODUCTION
Glycosidases are lysosomal enzymes that catalyze the hydrolysis of carbohydrate
moieties from polysaccharides and complex carbohydrates. Extracellular secretion
of lysosomal enzymes is an integral part of function in normal cells and
provides a mechanism for alteration of the cell surface and extracellular
matrix in pathologic and physiologic conditions [1,2]. Increased levels
of lysosomal hydrolases have been found in diseases associated with tissue
remodeling such as arthritis and muscular dystrophy. To our knowledge, expression
of lysosomal enzymes has not been studied during liver carcinogenesis. However,
glycosidases are induced by in vitro transformation of fibroblasts by DNA
and RNA viruses [3,4] and they are found at elevated levels in various tumors
[5].
The diesters of o-phthalate acid, the most widely used industrial plasticizers,
are ubiquitous low-level environmental contaminants. A study from the National
Toxicology program [6] found that di(2-ethylhexyl)-phthalate (DEHP) increased
the incidence of hepatocellular carcinomas and neoplastic nodules in rodents.
However, other studies have shown that DEHP suppressed the number and outgrowth
of enzyme altered preneoplastic foci that were positive for gamma glutamyl
transpeptidase (GGTase) in rats that were initiated with diethylnitrosamine
(DEN) [7], or in DEN initiated rats that were promoted by either phenobarbital
(PHB) or a choline deficient diet [8]. In contrast, di(n-octyl)phthalate
(DOP), a straight chain, stereoisomer of DEHP, was found to increase the
outgrowth of GGTase positive hepatic foci in rats initiated with DEN [9].
Since the mechanisms by which phthalates exert promoting and anti-promoting
activity on the development of preneoplastic GGTase positive foci are not
understood, it was of interest to determine if there was an association
between tumor promotion and lysosomal enzyme activities in this model.
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