Effect of polymerized toner on rat lung in chronic inhalation study.
In order to evaluate the chronic effect of polymerized toner particles on the lung, inflammation- and fibrosis-related genes were analyzed and 8-hydroxydeoxyguanosine (8-OHdG) was examined by using the lung tissue of rats subjected to 24 months of toner inhalation exposure. Wistar female rats were divided into four groups (5 weeks old, 30 rats in each): the high concentration exposure group (16.3 +/- 0.6 mg/m(3)), the medium concentration exposure group (4.4 +/- 0.3 mg/m(3)), the low concentration exposure group (1.6 +/- 0.2 mg/m(3)), and the control group (clean air). The material used was black toner, and its aerodynamic diameter in the exposure chamber was 3.0 microm. The rats were exposed to the material for 24 months (6 hours/day, 5 days/week) and dissected after the exposure period. RNA was extracted from one lung and the gene expression related to inflammation and fibrosis. Matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), and type I collagen were analyzed according to the ratio of each gene/beta-actin. Also, 8-OHdG level in the lung tissue was measured by HPLC with an electrochemical detector. Small fibrotic foci were found in the toner exposed groups; however, progressive or irreversible fibrosis was not found. The incidence of small fibrotic foci and cell aggregation increased in a dose-dependent manner. There were no significant differences of expression of MMP-2, TIMP-2, and type I collagen between the control group and each exposed group. Lung tumors did not develop in each group. A significant production of 8-OHdG was not observed in the toner exposed groups. In conclusion, toner produced by polymerization was not associated with evidence of carcinogenesis in this experiment.
Morimoto
Yasuo
Y
Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan. yasuom@med.uoeh.ac.jp
Hirohashi
Masami
M
Kasai
Takahiko
T
Oyabu
Takako
T
Ogami
Akira
A
Myojo
Toshihiko
T
Murakami
Masahiro
M
Nishi
Ken-ichiro
K
Kadoya
Chikara
C
Todoroki
Motoi
M
Yamamoto
Makoto
M
Kawai
Kazuaki
K
Kasai
Hiroshi
H
Tanaka
Isamu
I
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002908:Chronic Disease; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D019570:Inhalation Exposure; D007281:Ink; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D011108:Polymers / Q000633:toxicity*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics
D024042:Collagen Type I; D018076:DNA, Complementary; D011108:Polymers; D019716:Tissue Inhibitor of Metalloproteinase-2; D012313:RNA; D000080242:8-Hydroxy-2'-Deoxyguanosine; D020778:Matrix Metalloproteinase 2; D003849:Deoxyguanosine