DEVELOPMENT AND PERSISTENCE OF PLACENTAL GLUTATHIONE-S-TRANSFERASE POSITIVE FOCI IN LIVERS OF MALE F344 RATS EXPOSED TO O-NITROTOLUENE

Citation
Tt. Tori et al., DEVELOPMENT AND PERSISTENCE OF PLACENTAL GLUTATHIONE-S-TRANSFERASE POSITIVE FOCI IN LIVERS OF MALE F344 RATS EXPOSED TO O-NITROTOLUENE, Cancer letters, 95(1-2), 1995, pp. 167-173
Citations number
26
Categorie Soggetti
Oncology
Journal title
ISSN journal
03043835
Volume
95
Issue
1-2
Year of publication
1995
Pages
167 - 173
Database
ISI
SICI code
0304-3835(1995)95:1-2<167:DAPOPG>2.0.ZU;2-N
Abstract
In a previous 13-week study of o-nitrotoluene, a chemical-related incr ease in liver weight, hepatocellular vacuolization, and oval cell hype rplasia in male F344 rats was reported. In this study, the occurrence and change in number and size of hepatic foci in male F344 rats fed a diet containing 5000 ppm o-nitrotoluene or a control diet for 13 weeks , 26 weeks, and 13 weeks followed by a 13-week recovery period (26-wee k stop-exposure) were evaluated. The livers were stained immunohistoch emically for placental glutathione S-transferase (PGST), a marker of h epatic preneoplasia, and quantified stereologically using computer-ass isted image analysis. Exposure to o-nitrotoluene induced PGST-positive (PGST+) liver foci in all treatment groups. The 26-week continuous-ex posure group produced more PGST+ liver foci (961.4 foci/cm(3) versus 4 45.4 foci/cm(3)) and greater mean focus volume (4.34 mu m(3) versus 1. 34 mu m(3)) than the 13-week continuous-exposure group. In the 26-week stop-exposure group, there were fewer PGST+ liver foci (181.4 foci/cm (3)) than observed with continuous exposure at 13 weeks or 26 weeks; h owever, the mean focal volume in the stop-exposure group at 26 weeks ( 5.33 mu m(3)) was greater than that at 13 weeks (1.34 mu m(3)) or 26 w eeks of continuous exposure (4.34 mu m(3)). These findings demonstrate that (1) PGST+ foci are observed after only 13 weeks of exposure to o -nitrotoluene; (2) the number and size of foci increase with continued exposure for 26 weeks; and (3) although the number of PGST+ foci decr eases with time after chemical exposure is discontinued, many PGST+ fo ci do not regress but increase in size during the recovery period of 1 3 weeks. The persistence and increase in size of these foci, even in t he absence of chemical exposure, suggest the potential for a hepatocar cinogenic effect in long-term studies for o-nitrotoluene.