Lack of modifying effects of p-phenylenediamine on induction of gamma-glutamyl transpeptidase-positive foci in a medium-term bioassay system using F344 rats.
The modifying effects of p-phenylenediamine (p-PD) on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given p-PD at dietary levels of 1000, 330 and 110 parts per million (ppm), or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) at 600 ppm as a positive control for 6 weeks. At week 3 following DEN administration, all animals were subjected to partial hepatectomy. Slight retardation of body weight was observed in rats treated with p-PD at all dietary levels. Significant increases in relative liver weight were found in animals treated with 1000 ppm p-PD. Remarkable growth retardation and increased liver weight were found in rats given 3'-Me-DAB. p-PD did not significantly increase the level of gamma-glutamyl transpeptidase (gamma-GT) positive foci observed after DEN initiation. In contrast, 3'-Me-DAB demonstrated marked enhancing activity as evidenced by significantly increased values for gamma-GT positive foci as compared with the controls given DEN alone. The results demonstrate that p-PD does not modify liver carcinogenesis in our in vivo medium-term bioassay system.
Hagiwara
A
A
Daiyu-kai Institute of Medical Science, Ichinomiya, Japan.
Tamano
S
S
Shibata
M A
MA
Arai
M
M
Tsuda
H
H
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004052:Diethylnitrosamine / Q000633:toxicity*; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D006498:Hepatectomy; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010655:Phenylenediamines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis*
D010655:Phenylenediamines; D004052:Diethylnitrosamine; D005723:gamma-Glutamyltransferase; C029728:4-phenylenediamine