This Article Free Full Text (Free PDF) Free References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hard, G. C. Articles by Bucci, T. J. Search for Related Content PubMed PubMed Citation Articles by Hard, G. C. Articles by Bucci, T. J. Social Bookmarking                   What's this?

Rat Kidney Pathology Induced by Chronic Exposure to Fumonisin B1 Includes Rare Variants of Renal Tubule Tumor

American Health Foundation, Valhalla, New York 10595, gordonhard{at}msn.com

Paul C. Howard

National Center for Toxicological Research, Jefferson, Arkansas 72079

Robert M. Kovatch

Pathology Associates International, Jefferson, Arkansas 72079

Thomas J. Bucci

Pathology Associates International, Jefferson, Arkansas 72079

The carcinogenicity of fumonisin B₁ (FB₁), a worldwide contaminant of corn produced by Fusaria species of fungi, has been tested recently in 2-year feeding studies in Fischer F344 rats and B6C3F1 mice. Inclusion of FB₁ at 50 and 80 ppm in the diet induced liver tumors in female mice, and at 50 and 150 ppm induced renal tumors in male rats (22). In the present study, the kidneys from the rat bioassay were examined to characterize the various histopathological changes associated with renal tumor induction. In all high-dose (150 ppm) and mid-dose (50 ppm) male rats, and to a lesser extent in high-dose (100 ppm) female rats, there was evidence of sustained nephrotoxicity manifested as basophilia, apoptosis, cell regeneration, and simple tubule hyperplasia, affecting proximal convoluted tubules in the deep cortex, extending into the outer region of the outer stripe of outer medulla. A further alteration consisted of sporadic areas of interstitial hyalinization in deep cortex, suggestive of expanded basement membrane, coupled with tubule atrophy. The continued presence of nephrotoxicity throughout chronic exposure to FB₁ suggested that renal tumor development may have been an outcome of sustained cell loss and compensatory regeneration. In some cases, preneoplastic tubules or incipient renal tumors presented an immature or fetal form in association with interstitial hyalinization. The renal tubule tumors induced by FB₁ were typifi ed by a rare, highly malignant, anaplastic variant capable of growth by infi ltration. Of the 10 renal tubule tumors diagnosed in the mid-dose males, and the 16 in the high-dose males, 8 and 10, respectively, were graded as carcinomas. Anaplastic variants represented 50% of the mid-dose carcinomas and 80% of the high-dose carcinomas. One of the anaplastic carcinomas in a mid-dose male was a true sarcomatoid phenotype not previously recorded in the rodent. Metastatic invasion of the lung occurred with 25% of the mid-dose carcinomas and 50% of the high-dose carcinomas. It was speculated that FB₁ may have been influencing the growth characteristics of the induced renal tumors via its inhibitory action on the synthesis of sphingolipids, which in turn, participate in regulating cell contact, growth, and differentiation, or alternatively by affecting cell adhesion molecules.

Key Words: Adenoma • apoptosis • atypical tubule hyperplasia • carcinoma • metastases • mycotoxin • nephrotoxicity

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. C. Hard, J. C. Seely, G. E. Kissling, and L. J. Betz Spontaneous Occurrence of a Distinctive Renal Tubule Tumor Phenotype in Rat Carcinogenicity Studies Conducted by the National Toxicology Program Toxicol Pathol, April 1, 2008; 36(3): 388 - 396. [Abstract] [Full Text] [PDF]