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Polycyclic aromatic hydrocarbons and possible metabolites: Convertogenic activity in yeast and tumor initiating activity in mouse skin

Polycyclische aromatische Kohlenwasserstoffe und mögliche Metaboliten: Konvertogene Wirkung bei Hefe und Tumor-initiierende Wirkung an der Mäusehaut

Summary

The diploid respiratory-deficient strain of yeast D4-RDII was used to assay PAH and urethane as well as some oxygenated derivatives of PAH and the (aliphatic) epoxide hydrolase inhibitor TCPO for convertogenic (mutagenic) activity. As a positive control, the convertogenic ultimate rat liver carcinogen NOAcAAF was used. PAH and urethane were found inactive as convertogens, TCPO was weakly active, whereas oxygenated electrophilic derivatives of PAH, such as K-region oxides, were found strong convertogens. For comparison, some convertogenic key compounds were assayed for their tumorinitiating activity in mouse skin in the standardized system using TPA as a promoter. PAH were stronger initiators than all oxygenated derivatives of PAH tested. TCPO alone exhibited very weak, if any, initiating activity. It was unable to modify initiation to any significant extent, if administered 5 min prior to administration of an initiator.

In the absence of correlation between convertogenic and initiating activity the question of the chemical nature of “ultimate initiators” of mouse skin carcinogenesis awaits further investigation.

Zusammenfassung

Am atmungsdefizienten diploiden Hefestamm D4-RDII wurde die konvertogene (mutagene) Wirkung von PAH, Urthan, einigen sauerstoffhaltigen PAH-Derivaten und des (aliphatischen) Epoxidhydrolase-Inhibitors TCPO untersucht. Als positive Kontrolle diente die konvertogene “Wirkform” des Rattenlebercarcinogens NOAcAAF. PAH und Urethan waren nicht konvertogen, TCPO zeigte eine geringe Wirkung, während elektrophile PAH-Derivate wie die K-Region-Oxide stark konvertogen wirkten. Einige konvertogene Schlüsselsubstanzen wurden zum Vergleich auf ihre tumorinitiierende Wirkung an der Mäusehaut im standardisierten Experiment mit TPA als Promoter geprüft. PAH erwiesen sich als stärkere Initiatoren als alle ihre entsprechenden sauerstoffhaltigen Derivate. TCPO allein zeigt—wenn überhaupt — nur geringe Wirkung. Wenn TCPO 5 min vor einem Initiator appliziert wurde, hatte es keinen nennenswerten Einfluß auf die Initiation.

Auf Grund der mangelnden Korrelation zwischen konvertogener und initiierender Wirkung sind weitere Untersuchungen zum Problem der chemischen Natur der „Wirkformen” von Initiatoren der Carcinogenese der Mäusehaut erforderlich.

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Abbreviations

DBA:

dibenz(a,h)anthracene

DMBA:

7,12-dimethylbenz(a)anthracene

DMSO:

dimethylsulfoxide

MBA:

methylbenz(a)anthracene

NOAcAAF:

N-acetoxy-N-2-acetylaminofluorene

NOHAAF:

N-hydroxy-N-2-acetylaminofluorene

PAH:

polycyclic aromatic hydrocarbon(s)

TCPO:

1,2-epoxy-3,3,3-trichloropropane

TLC:

thin-layer chromatography

TPA:

12-O-tetradecanoylphorbol-13-acetate

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Corresponding author

Correspondence to E. Hecker.

Additional information

In part PhD-thesis of H. Friesel (Friesel 1978)

This investigation was supported, in part, by grants III B 4-7291-MT 403 a and 307-7291-MT-424 of the Bundesminister für Forschung und Technologie, Bonn, Federal Republic of Germany, under a joint contract with the Institut für Biochemie, Deutsches Krebsforschungszentrum, Heidelberg

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Siebert, D., Marquardt, H., Friesel, H. et al. Polycyclic aromatic hydrocarbons and possible metabolites: Convertogenic activity in yeast and tumor initiating activity in mouse skin. J Cancer Res Clin Oncol 102, 127–139 (1981). https://doi.org/10.1007/BF00410664

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Key words

  • Polycyclic aromatic hydrocarbons
  • K-region oxides
  • Gene conversion in yeast
  • Tumor initiation in mouse skin
  • Ultimate carcinogens
  • Ultimate initiators

Schlüsselwörter

  • Polycyclische aromatische Kohlenwasserstoffe
  • K-Region-Oxide
  • Genkonversion in Hefe
  • Tumor-Initiation an der Mäusehaut
  • Wirkformen von Carcinogenen
  • Wirkformen von Initiatoren