Synergism of environmental carcinogens and promoters on bladder cancer development initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine in F344 rats.
Synergistic or additive effects of combined treatments with carcinogens or promoters on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-initiated rat bladder carcinogenesis were examined. Male F344 rats were given BBN as an initiator followed by low doses of 3 sodium salts (sodium bicarbonate, sodium L-ascorbate and sodium citrate) and/or 3 antioxidants (butylated hydroxyanisole, butylated hydroxytoluene and tertiary butylhydroxyquinone). Combined treatments with 3 sodium salts or 3 antioxidants, and especially all 6 chemicals together promoted bladder carcinogenesis. In addition, these combined treatments were associated with increased DNA synthesis of the bladder epithelium. Combined administration of the carcinogens, o-anisidine, p-cresidine, and 4-chloro-o-phenylenediamine at low doses also enhanced BBN-initiated bladder carcinogenesis. These results indicate that environmental carcinogens or promoters can exert synergistic or additive actions on bladder cancer induction.
Ono
S
S
First Department of Pathology, Nagoya City University Medical School.
Kurata
Y
Y
Shichino
Y
Y
Sano
M
M
Fukushima
S
S
D000818:Animals; D001835:Body Weight; D002085:Butylhydroxybutylnitrosamine; D002273:Carcinogens; D004273:DNA, Neoplasm / Q000378:metabolism; D004357:Drug Synergism; D004785:Environmental Pollutants / Q000633:toxicity*; D005247:Feeding Behavior; D008297:Male; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*
D002273:Carcinogens; D004273:DNA, Neoplasm; D004785:Environmental Pollutants; D002085:Butylhydroxybutylnitrosamine