Metabolism of 4,4'-Methylene-bis(2-chloroaniline) in Explant Cultures of Human and Dog Bladder and Dog Liver Cell Cultures.
Studies of the consequences of exposure to 4,4'-methylene-bis(2- chloroaniline) (101144) (MOCA) were made, including an investigation of the metabolism, DNA binding, and DNA adduct formation in human and dog tissues. Human tissues were obtained at autopsy or surgery and cultured. Cultured human and dog bladder tissues were exposed to 0.1, 1 and 10 micromolar radiolabeled MOCA. The binding of MOCA to the DNA of dog bladder explants appeared to be dose related with the binding levels being approximately one half those of 2- acetylaminofluorene (AAF). Four adducts were formed between MOCA metabolites and dog bladder DNA. A dose related binding of MOCA to DNA was noted in human bladder explants with the binding levels being approximately equal to those in dog bladder explants. The binding of MOCA to the DNA of dog explants was higher than that to the DNA of dog and human bladder explants. Studies were also undertaken of benzotrichloride (98077) (BTC) which was injected intraperitoneally 24 times during a period of 8 weeks causing lung tumors in strain-A mice. BTC was about as active as benzo(a)pyrene and seven times more active than urethane as an inducer of lung tumors.
Animal-studies; Humans; Arylamines; Nucleic-acids; Carcinogens; Mutagens; Metabolic-study; Bladder-cancer; Lung-cancer; Anilines; In-vitro-studies;
Proceedings of the Fourth NCI/EPA/NIOSH Collaborative Workshop: Progress on Joint Environmental and Occupational Cancer Studies, April 22-23, 1986, Rockville, Maryland, NIH Publication No. 88-2960