Find results with:

Add another field

Search by date

to

Searching collections:

Dartmouth Dissertations

Add or remove collections

Home Dartmouth Dissertations Page 1

Reference URL

To link to the entire object, paste this link in email, IM or document

To embed the entire object, paste this HTML in website

To link to this page, paste this link in email, IM or document

To embed this page, paste this HTML in website

Hepatic toxicity and compensatory hyperplasia in a rat model of aflatoxin bi-induced liver cancer

you wish to report:

Your comment:

Your Name:

Submit

Cancel

...

Back to top

Powered by CONTENTdm®

Call No.	RC280.L5 M39 1996
Author	Maxuitenko, Yulia Y.
Title	Hepatic toxicity and compensatory hyperplasia in a rat model of aflatoxin bi-induced liver cancer
Date	1996
Abstract	A hypothesis that chronic aflatoxin Bi- (AFBi) induced hepatotoxicity and the resulting compensatory cell proliferation are critical for the growth of preneoplastic lesions was investigated. A commonly utilized protocol which consists of 10 doses of AFBi (five consecutive days per week for two weeks ) given by gavage to weanling rats at a level of 25 jig/dose was used. The highest level of AFBi-induced hepatotoxicity was observed after the first two doses of AFBi. Putative preneoplastic, glutathione S-transferase positive (GST-P+) foci started to appear during the first week of the AFBi treatment. The foci continued to increase in number and size during the first five weeks after the end of the AFBi treatment, at which time the volume per cent of the GST-P+ foci reached a plateau that lasted at least for two months. The AFBi treatment inhibited DNA synthesis in the parenchymal cells, yet caused a transient increase in proliferation of bile duct cells (BDC). This burst of BDC proliferation subsided by the end of the first week of the AFBi treatment. The usefulness of urinary taurine as a non-invasive measure of AFBi-induced hepatotoxicity was evaluated. Changes in urinary taurine in both acute toxicity and low dose sub-chronic exposure experiments were characterized. Urinary taurine was insensitive to the amount of hepatic damage caused by low acute doses of AFBi (0.25-0.5 mg/kg) or during low level sub-chronic AFBi treatment. Taurine was only elevated by high levels of hepatotoxicity. BDC proliferation, on the other hand, appeared to be sensitive to the amount of hepatic damage caused by low doses of AFBi and was ii used as a measure of hepatotoxicity to screen dithiolethiones for their cancer chemopreventive efficacy. There was a significant correlation (p<0.01) between changes in BDC proliferation and chemoprevention of AFBi-induced foci formation. These results imply that inhibition of AFBi-induced hepatotoxicity affords protection against preneoplastic foci development. Based on these results, the extent of protection from acute AFBi-induced hepatotoxicity offers a simple, short term, biological endpoint to screen dithiolethiones for their chemopreventive properties.
Description	xvii, 207 p. leaves : ill. (some col.)
Format	application/pdf
Advisor	Roebuck, Bill D.
Subject	Liver -- Cancer -- Etiology. Hepatotoxicology. Aflatoxins -- Toxicology. Taurine. Liver -- Cancer -- Animal models.
College	Dartmouth Medical School -- Department of Pharmacology and Toxicology.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.1515

Title	Page 1
Full Text	HEPATIC TOXICITY AND COMPENSATORY HYPERPLASIA IN A RAT MODEL OF AFLATOXIN Bi-INDUCED LIVER CANCER A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Pharmacology and Toxicology by Yulia Y. Maxuitenko DARTMOUTH COLLEGE Hanover, New Hampshire May 1996

Find results with:

Searching collections:

Home Dartmouth Dissertations Page 1

Hepatic toxicity and compensatory hyperplasia in a rat model of aflatoxin bi-induced liver cancer

Object Description

Description

Hepatic toxicity and compensatory hyperplasia in a rat...

Hepatic toxicity and compensatory hyperplasia in a rat...

	All
	Pages Enter page numbers or page ranges separated by commas. For example: 1,3,5-12