Summary
To obtain some initial evidence on the mechanism(s) of activation of PAH in rat mammary gland, we studied the carcinogenicity of a series of PAH directly applied to this tissue. A series of PAH which are or are not expected to be activated by one-electron oxidation because of their low or high ionization potential (IP), respectively, were tested. The compounds were dispersed as fine powders on an exposed mammary gland of female Sprague-Dawley rats. 5-Methylchrysene, dibenz[a,h]anthracene and benz[a]anthracene, which have relatively high IP, were inactive. In contrast, three PAH with relatively low IP, 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene (BP), and 3-methylcholanthrene (MC), were potent carcinogens. 6-MethylBP, with low IP, and 7-methylbenz[a]anthracene, with borderline IP, elicited only mesenchymal tumors, whereas BP 7,8-dihydrodiol and cyclopenta[cd]pyrene were inactive. A series of MC derivatives substituted at C-1 or C-2 was tested. Substituents at C-1, the position of activation in the one-electron oxidation pathway, generally suppressed carcinogenic activity. Substitution at C-2 did not eliminate carcinogenic activity, w9th the exception of MC-2-one. These results provide initial information suggesting that one-electron oxidation may be a mechanism of activation for PAH in the mammary gland.
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Abbreviations
- BP:
-
benzo[a]pyrene
- BP 7,8-dihydrodiol:
-
7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene
- DMBA:
-
7,12-dimethylbenz[a]anthracene
- 1-hydroxyMC:
-
1-hydroxy-3-methylcholanthrene
- 2-hydroxyMC:
-
2-hydroxy-3-methylcholanthrene
- IP:
-
Ionization potential(s)
- MC:
-
3-methylcholanthrene
- MC-1-one:
-
3-methylcholanthrene-1-one
- MC-2-one:
-
3-methylcholanthrene-2-one
- MCL:
-
3-methylcholanthrylene
- 1-methylMC:
-
1,3-dimethylcholanthrene
- 2-methylMC:
-
2,3-dimethylcholanthrene
- 6-methylBP:
-
6-methylbenzo[a]pyrene
- PAH:
-
polycyclic aromatic hydrocarbons(s)
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Supported by Public Health Service contract NO1 CP05620 and grants 1RO1 CA32376 and Laboratory Cancer Research Center Core Grant CA36727 from the National Cancer Institute
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Cavalieri, E., Rogan, E. & Sinha, D. Carcinogenicity of aromatic hydrocarbons directly applied to rat mammary gland. J Cancer Res Clin Oncol 114, 3–9 (1988). https://doi.org/10.1007/BF00390478
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DOI: https://doi.org/10.1007/BF00390478