Target organ specificity of cell proliferation induced by various carcinogens.
The target organ specificities of cell proliferation and histopathological lesion induction by 5 carcinogens having different target organs were evaluated using a multiorgan carcinogenesis bioassay. In Group 1, male F-344 rats aged 6 wk were sequentially treated with N-diethylnitrosamine (DEN, single 100-mg/kg ip injection, week 0), N-methyl-N-nitrosourea (MNU, 4 20-mg/kg ip injections, weeks 0-2), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN, 0.05% in drinking water, weeks 0-2), N,N'-dimethylhydrazine (DMH, 4 40-mg/kg sc injections, weeks 2-4), and dihydroxy-di-N-propylnitrosamine (DHPN, 0.1% in drinking water, weeks 2-4) during the first 4 wk. In Groups 2-6, rats were treated with only one of the above initiators, applied as in Group 1. Group 7 served as the no-treatment control. Bromouracil deoxyriboside (BUdR) labeling indices (LI) were counted in various organs at weeks 2 and 4. Numbers and areas of glutathione S-transferase placental form positive (GST-P+) liver foci were measured at weeks 2, 4, and 28. Preneoplastic or neoplastic lesion development was assessed at week 28. With regard to specific elevation of cell proliferation in target organs, BUdR LIs in the urinary bladder, liver, and colon were, respectively, increased in the BBN alone, DEN alone, and DMH alone treated groups as well as in Group 1. However, LIs of thyroid, lung, and kidney were also elevated by several carcinogens not including these organs in their carcinogenic target specificity. On the other hand, morphological lesions and GST-P+ foci were limited to Group 1 and the target organs of the corresponding carcinogen-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Yoshida
Y
Y
First Department of Pathology, Nagoya City University Medical School, Japan.
Tatematsu
M
M
Takaba
K
K
Iwasaki
S
S
Ito
N
N
D019813:1,2-Dimethylhydrazine; D000818:Animals; D001973:Bromodeoxyuridine; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D004127:Dimethylhydrazines / Q000494:pharmacology; D004357:Drug Synergism; D005982:Glutathione Transferase / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D008770:Methylnitrosourea / Q000494:pharmacology; D009602:Nitrosamines / Q000494:pharmacology; D009928:Organ Specificity / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D004127:Dimethylhydrazines; D009602:Nitrosamines; D008770:Methylnitrosourea; D005982:Glutathione Transferase; D001973:Bromodeoxyuridine; D019813:1,2-Dimethylhydrazine