Co-carcinogenic effects of NaHCO3 on o-phenylphenol-induced rat bladder carcinogenesis.
The role of urinary pH and Na+ concentration on the bladder carcinogenesis of o-phenylphenol (OPP) was examined in male F344 rats. The rats were given powdered diet containing 2% sodium o-phenylphenate (OPP-Na, group 1), 1.25% OPP plus 0.64% NaHCO3 (group 2), 1.25% OPP plus 0.32% NaHCO3 (group 3), 1.25% OPP plus 0.16% NaHCO3 (group 4), 1.25% OPP (group 5), 0.64% NaHCO3 (group 6) or no test chemical (group 7) for 104 weeks respectively. Incidences of bladder carcinoma induced were significantly higher in groups 1 (12 of 29 rats, 41.4%) and 2 (9 of 29 rats, 31.0%) than in group 7 (0 of 27 rats, 0%). Groups 3 and 4 induced bladder carcinomas in 4 of 29 rats (13.8%) and 4 of 26 rats (15.4%) respectively, whereas no tumors occurred in group 5 (0 of 27, 0%). The incidence in group 6 was 3.6% (1 of 28 rats). Groups 1 and 2 induced significant increases in urinary pH and Na+ concentrations, whereas group 5 did not. Groups 3 and 4 showed the same tendency as groups 1 and 2. Examination with a scanning electron microscope showed the appearance of pleomorphic microvilli, short, uniform microvilli, and ropy or leafy microridges on the luminal surface of the bladder in groups 1-5 of rats treated with OPP or OPP-Na for 8 weeks. The appearance and severity were the same in groups 1 and 2, followed by the groups with decreasing doses of NaHCO3. The results indicated that OPP-Na is carcinogenic for the rat bladder, but OPP is not. However, increased urinary pH and Na+ concentration play important roles in OPP-Na rat bladder carcinogenesis.
Fukushima
S
S
First Department of Pathology, Nagoya City University Medical School, Japan.
Inoue
T
T
Uwagawa
S
S
Shibata
M A
MA
Ito
N
N
D000818:Animals; D001639:Bicarbonates / Q000633:toxicity*; D001713:Biphenyl Compounds / Q000633:toxicity*; D002273:Carcinogens; D002277:Carcinoma / Q000139:chemically induced / Q000473:pathology; D005659:Fungicides, Industrial / Q000633:toxicity*; D006863:Hydrogen-Ion Concentration; D006965:Hyperplasia; D008297:Male; D010212:Papilloma / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000633:toxicity*; D017693:Sodium Bicarbonate; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology; D014556:Urine
D001639:Bicarbonates; D001713:Biphenyl Compounds; D002273:Carcinogens; D005659:Fungicides, Industrial; D017693:Sodium Bicarbonate; D012964:Sodium; C004369:2-phenylphenol