Effect of Feeding 7OH-2-Acetaminofluorene to Albino Rats

Hoch-Ligeti, Cornelia

doi:10.1038/bjc.1947.37

Cited by 21 publications

(6 citation statements)

References 1 publication

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“…Aroclor 1254 induces a number of xenobiotic oxidative activities [Alvares et al, 1973; Litterst and van Loon, 1974; Ecobichon and Comeau, 1974;Ong et al, 19801. Since ring oxidation of arylamines and arylamides is generally considered to be a detoxification process [Bielschowslq, 1947;Hoch-Ligeti, 1947; Morris et al, 1960;McCann et al, 19751, the induction of the activities that form these metabolites may decrease the mutagenicity of these agents.…”

Section: Discussionmentioning

confidence: 99%

Metabolism of 2‐acetylaminofluorene in the chinese hamster ovary cell mutation assay

Heflich¹,

Djurić

Zhuo

et al. 1988

Environ and Mol Mutagen

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Chinese hamster ovary (CHO) cells were exposed to 2-acetylaminofluorene (2-AAF) and 2-aminofluorene (2-AF), and several of their N-oxidized metabolites in order to study the mechanisms by which arylamides and arylamines produce mutations in mammalian cells. The number of mutations induced at the hypoxanthine-guanine phosphoribosyl transferase locus by each compound (mutants/10(6) CHO cells/nmol compound/ml) was estimated to be: N-acetoxy-2-AAF, 310; N-hydroxy-2-AF, 3; N-hydroxy-2-AAF (with and without hepatic S9 activation), 0.7; 2-AAF (with S9), 0.1; and 2-AF (with S9), 0.09. With each compound, DNA adducts were also identified and quantified, and in all cases the major adduct was N-(deoxyguanosin-8-yl)-2-AF. 2-AAF and N-hydroxy-2-AAF also formed minor amounts of N-(deoxyguanosin-8-yl)-2-AAF and 3-(deoxyguanosin-N2-yl)-2-AAF. The relationship between mutation induction and adduct formation for each of the derivatives was similar to that previously reported for N-hydroxy-2-AF. Inclusion of the deacetylase inhibitor, paraoxon, reduced the mutagenicity of 2-AAF, N-hydroxy-2-AAF and N-acetoxy-2-AAF, and the DNA adducts produced by N-acetoxy-2-AAF to background levels. Acetyl coenzyme A increased the mutations and CHO cytosol-mediated DNA binding of N-hydroxy-2-AAF, but did not substantially increase these responses from N-hydroxy-2-AF. N-Hydroxy-2-AAF was not detectably metabolized by CHO cells. Taken together, these data indicate that CHO cells metabolized N-acetoxy-2-AAF to a reactive derivative by N-deacetylation to N-acetoxy-2-AF, while N-hydroxy-2-AF reacted directly with DNA. The major pathway of N-hydroxy-2-AAF activation appeared to be an initial O-acetylation to N-acetoxy-2-AAF and this occurred to only a limited extent in the CHO cells. N-Hydroxy-2-AAF also seemed to form an additional unknown ester intermediate that gave rise to acetylated DNA adducts. The initial step in the activation of 2-AAF and 2-AF was an N-oxidation to N-hydroxy-2-AAF and N-hydroxy-2-AF, respectively. The limited O-acetylase activity in CHO cells appeared to contribute to the low sensitivity of these cells toward mutation induction by arylamines and arylamides.

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Section: Discussionmentioning

confidence: 99%

Metabolism of 2‐acetylaminofluorene in the chinese hamster ovary cell mutation assay

Heflich¹,

Djurić

Zhuo

et al. 1988

Environ and Mol Mutagen

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“…Succinoxidase activity of rat liver slices decreased when p-dimethylaminoazobenzene was fed and was even lower in the resulting tumors. This decrease in activity was prevented by diets that retard carcinogenesis (183). A similar decrease in enzyme was not observed when homogenates were used in place of liver slices or when 2-acetylaminofluorene was fed (184).…”

Section: Tissue Changes In Neoplasiamentioning

confidence: 71%

The Biochemistry of Carcinogenesis

Rusch¹,

LePage²

1948

Annu. Rev. Biochem.

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“…Whether the difference in enlargement of the adrenals in the two irradiated groups is real is difficult to decide, as only the male rats of the hard irradiated group could be used for this comparison; female rats have always larger adrenals than males. In previous experiments (Hoch-Ligeti, 1947, 1948 on the effect of the adnministration of small doses of penetrating and soft X-rays on healthy rats it was found that the increases in adrenal weights of male rats were significant in both cases.…”

Section: Resultsmentioning

confidence: 91%

Effects of Repeated X-Radiation of the Whole Body on the Development of Tumours in Rats Due to Feeding p-Dimethylaminoazobenzene

Hoch-Ligeti¹

1949

Br J Cancer

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Effect of Feeding 7OH-2-Acetaminofluorene to Albino Rats

Cited by 21 publications

References 1 publication

Metabolism of 2‐acetylaminofluorene in the chinese hamster ovary cell mutation assay

Metabolism of 2‐acetylaminofluorene in the chinese hamster ovary cell mutation assay

The Biochemistry of Carcinogenesis

Effects of Repeated X-Radiation of the Whole Body on the Development of Tumours in Rats Due to Feeding p-Dimethylaminoazobenzene

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