Hepatic tumorigenesis

Peraino, C., Fry, R. J., Staffeldt, E., and Christopher, J. P. (1975). Comparative enhancing effects of phenobarbital, amobarbital, diphenylhydantoin, and dichlorodiphenyltrichloroethane on 2-acetylami-nofluorene-induced hepatic tumorigenesis in the rat. Cancer Res 35(10), 2884—2890. 

Ito, Y, Yamanoshita, O., Asaeda, N., Tagawa, Y, Lee, C. H., Aoyama, T., Ichihara, G., Ftiruhashi, K., Kamijima, M., Gonzalez, E. J., and Nakajima, T. (2007). Di(2-ethylhexyl)phthalate induces hepatic tumorigenesis through a peroxisome proliferator-activated receptor alpha-independent pathway. J Occup Health 49, 172-182. 

Rao, M. S., Lalwani, N. D., Watanabe, T. K., and Reddy, J. K. (1984). Inhibitory effect of antioxidants ethoxyquin and 2(3)-tert-butyl-4-hydroxyanisole on hepatic tumorigenesis in rats fed ciprofibrate, a peroxisome proliferator. Cancer Res 44, 1072-1076. 

Boyd, J. N., Babish, J. G., an4v Stoewsand, G. S., 1982, ModiEcation by beet and cabbage diets of aflatoxin Bi-inducea rat plasma a-fetoprotein elevation, hepatic tumorigenesis, and mutagenicity of urine. Food Chem. Toxicol. 20 47. 

The role of N-sulfonyloxy arylamines as ultimate carcinogens appears to be limited. For N-hydroxy-2-naphthylamine, conversion by rat hepatic sulfotransferase to a N-sulfonyloxy metabolite results primarily in decomposition to 2-amino-l-naphthol and 1-sulfonyloxy-2-naphthylamine which are also major urinary metabolites and reaction with added nucleophiles is very low, which suggests an overall detoxification process (9,17). However, for 4-aminoazobenzene and N-hydroxy-AAF, which are potent hepatocarcinogens in the newborn mouse, evidence has been presented that strongly implicates their N-sulfonyloxy arylamine esters as ultimate hepatocarcinogens in this species (10,104). This includes the inhibition of arylamine-DNA adduct formation and tumorigenesis by the sulfotransferase inhibitor pentachlorophenol, the reduced tumor incidence in brachymorphic mice that are deficient in PAPS biosynthesis (10,115), and the relatively low O-acetyltransferase activity of mouse liver for N-hydroxy-4-aminoazobenzene and N-OH-AF (7,114,115). 

Soyka LF. 1980. Hepatic drug metabolizing enzyme activity and tumorigenesis in mice following perinatal exposure to benzo(a)pyrene. Pediatr Pharmacol 1 85-96. 

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