Robert G. Neumann: A Failure to Negotiate

Neumann, Robert; Bishara, Ghassan

doi:10.2307/2536747

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“…They are mutagenic, and their reactive metabolites bind to DNA. However, DNA damage as measured by covalent DNA binding does not correlate well with organotropism (1,2). The highest levels of DNA-bound metabolites of trans-4-aminostilbene derivatives in rats are always found in liver, which is a nontarget tissue (3,4).…”

Section: Introductionmentioning

confidence: 99%

Induction of single‐strand breaks and interstrand cross‐links in liver DNA after the administration of 2‐acetylaminofluorene and trans‐4‐acetylaminostilbene to rats

Ruthsatz

Neumann

1987

J. Biochem. Toxicol.

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2-Acetylaminofluorene (AAF) or trans-4-acetylaminostilbene (AAS) was orally or intraperitoneally administered to female Wistar rats. DNA from liver cells was analyzed for single-strand breaks by the alkaline elution assay. Only borderline effects were observed with doses (100 mumol/kg) used in animal carcinogenesis experiments. Even high doses of AAF (1,000 mumol/kg) were not effective. Methyl methanesulfonate (MMS) in vivo and gamma irradiation in vitro were shown to produce dose-dependent DNA single-strand breaks (positive control). Only a marginal effect was obtained with 100 mumol/kg MMS. The elution rate of DNA was increased by a factor of 34 in liver cells in vitro with 400 rad of gamma irradiation. Only a fraction of this rate could be demonstrated immediately after irradiation in vivo, and no lesions were found two hours later. This strongly indicates the rapid repair of single-strand breaks. Additional experiments showed that AAS, a nonhepatocarcinogen, produced more interstrand cross-links in the rat liver DNA than did AAF.

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