Further evidence for the involvement of inhibition of cell proliferation and development in thymic and splenic atrophy induced by the peroxisome proliferator perfluoroctanoic acid in mice

Citation
Q. Yang et al., Further evidence for the involvement of inhibition of cell proliferation and development in thymic and splenic atrophy induced by the peroxisome proliferator perfluoroctanoic acid in mice, BIOCH PHARM, 62(8), 2001, pp. 1133-1140
Citations number
47
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
8
Year of publication
2001
Pages
1133 - 1140
Database
ISI
SICI code
0006-2952(20011015)62:8<1133:FEFTIO>2.0.ZU;2-V
Abstract
We recently demonstrated that severe thymic and splenic atrophy occur upon dietary treatment of mice with potent peroxisome proliferators (PPs), e.g. perfluorooctanoic acid (PFOA), WY-14,643, nafenopin, and di(2-ethylhexyl)ph thalate (DEHP). In the present study, we investigated this phenomenon furth er employing a relative inert PP, PFOA. Comparison of the dose-dependencies and time-courses indicated that the peroxisome proliferative effect occurr ed prior to atrophy of both the thymus and spleen. However, following withd rawal of PFOA from the diet, the weight of the thymus and spleen rapidly re turned to normal within 10 and 5 days, respectively, in contrast to the mor e persistent peroxisome proliferation. Furthermore, the changes in thymus a nd spleen weight upon PFOA treatment and the following withdrawal from diet paralleled the changes in total thymocyte and splenocyte counts, respectiv ely. It was found previously that the decreases in the thymocyte population s present in the S and G2/M phases, as well as in the number of CD4(+)CD8() cells upon PFOA treatment, were the most dramatic, perhaps reflecting inh ibition of thymocyte proliferation in connection with thymocyte development . Here, the recovery of thymocytes began with increases in the populations in these same phases of the cell cycle, with CD4(+)CD8(+) cells recovering most rapidly, lending further support to our previous hypothesis. The possi ble relationship of these immunotoxic effects of PPs to the changes they ca use in fatty acid metabolism is discussed. (C) 2001 Elsevier Science Inc. A ll rights reserved.