Investigations on cell proliferation in B6C3F(1) mouse liver by diethanolamine.
Diethanolamine (DEA) has been shown to induce liver tumours in B6C3F(1) mice in a previous 2-year dermal study. To elucidate the mode of action groups of eight male and eight female B6C3F1 mice were dermally exposed to daily DEA doses of 0 or 160 mg/kg body weight/day for 1 week. Reversibility was assessed after a 3-week treatment-free recovery period. Subsequently groups of 10 male B6C3F(1) mice were dermally exposed to daily DEA doses of 0 or 160 mg/kg body weight for 1, 4 or 13 weeks. Finally, groups of 8 male B6C3F(1) mice were dermally exposed to daily DEA doses of 0, 10, 20, 40, 80, and 160 mg/kg body weight for 1 and 13 weeks. Following a 1-week treatment, DEA caused increased cell proliferation (5-bromo-2'-deoxyuridine (BrdU) method) in zone 3 (central vein region) of the liver lobules at 160 mg/kg body weight. Reversibility of liver cell proliferation was demonstrated in the recovery phase. In the subsequent studies increased cell proliferation was observed at 10 mg/kg body weight or higher after 13 weeks of treatment. These results support the hypothesis that sustained liver cell proliferation is a potential non genotoxic mode of action by which DEA promotes liver tumours in B6C3F(1) mice.
Mellert
W
W
BASF Aktiengesellschaft, Product Safety, Z 470, D-67056 Ludwigshafen, Germany.
Kaufmann
W
W
Rossbacher
R
R
van Ravenzwaay
B
B
D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001973:Bromodeoxyuridine; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects
D002273:Carcinogens; D004983:Ethanolamines; D004247:DNA; C020283:diethanolamine; D001973:Bromodeoxyuridine