The metabolism of repeatedly administered trans-4-dimethylaminostilbene and 4-dimethylaminobibenzyl

Neumann, Hans‐Günter

doi:10.1007/bf00284340

Cited by 6 publications

(1 citation statement)

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“…It induces drug metabolizing enzymes (18)(19)(20) and thus shares a trait common to other typical promoters, and it is also toxic to liver tissue. Trans-AAS, in contrast, neither induces enzymes (21) nor is toxic to liver, even in lethal doses (7).…”

Section: Discussionmentioning

confidence: 89%

Role of tissue exposure and DNA lesions for organ-specific effects of carcinogenic trans-4-acetylaminostilbene in rats.

Neumann¹

1983

Environ Health Perspect

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trans-4-Acetylaminostilbene is acutely toxic to the glandular stomach and produces sebaceous gland tumors in rats quite specifically. Metabolism, tissue exposure to reactive metabolites, DNA binding and persistence of DNA lesions are implicated in tissue susceptibility, but nothing indicates that one of these parameters determines the biological effect. All tissues are exposed to reactive metabolites, liver as a nontarget tissue ranking highest. DNA binding in this tissue, however, is not irrelevant to tumor formation, but rather indicates the presence of initiating lesions. They can be amplified by partial hepatectomy and/or promoters, such as phenobarbital, DDT and diethylstilbestrol. Liver tumors are formed in high yields with these treatments, and mammary tumors also occur. trans-4-Acetylaminostilbene is therefore considered to be an incomplete carcinogen in these tissues and may initiate cells in other tissues as well. Apparently it lacks promoting properties which are supposed to be unrelated to reactive metabolites. It is concluded that DNA lesions do not reflect tissue risk, but rather secondary effects ultimately determine where the process of tumor formation starts and how fast it develops.

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Section: Discussionmentioning

confidence: 89%