A possible role for cell proliferation in potassium bromate (KBrO3) carcinogenesis.
Accumulation of alpha 2u-globulin and induction of cell proliferation were examined in kidneys of rats exposed to KBrO3, KBr or NaBrO3 in their drinking water. Hyaline droplets observed after KBrO3 or NaBrO3 administration to male rats were specifically immunostained for alpha 2u-globulin. Increases in cell proliferation were found in the proximal tubules of male rats given KBrO3 or NaBrO3 but not KBr for 2, 4, and 8 weeks. No such change was evident in KBrO3-treated female rats or the distal tubules of any treated animal. The concordance between hyaline droplet accumulation and increased cell turnover suggests that KBrO3- and NaBrO3-induced cell replication in kidneys of male rats may result from alpha 2u-globulin nephropathy. Considering the fact that KBrO3 has genotoxic potential involving oxidative stress, we hypothesize that the induced cell proliferation might predominantly play an additive role in its carcinogenesis. Furthermore, the present data, showing similar effects of NaBrO3 on the rat kidney, are of direct significance to its risk assessment.
Umemura
T
T
Division of Toxicology, National Institute of Health Sciences, Tokyo, Japan.
Sai
K
K
Takagi
A
A
Hasegawa
R
R
Kurokawa
Y
Y
D000510:Alpha-Globulins / Q000187:drug effects; D000818:Animals; D001959:Bromates / Q000633:toxicity*; D001965:Bromides / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005503:Food Additives / Q000633:toxicity*; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011188:Potassium / Q000633:toxicity; D017680:Potassium Compounds; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000633:toxicity; D017670:Sodium Compounds
D000510:Alpha-Globulins; D001959:Bromates; D001965:Bromides; D002273:Carcinogens; D005503:Food Additives; D017680:Potassium Compounds; D017670:Sodium Compounds; C019536:potassium bromate; D012964:Sodium; C039004:potassium bromide; D011188:Potassium; C060553:sodium bromate