Mutagenicity of cyclopenta-fused polynuclear aromatic hydrocarbons and a non-polar fraction from a fuel combustion sample in a Salmonella forward mutation assay without exogenous metabolic activation

• Published in: Mutation research Vol. 391; no. 3; pp. 117 - 125
• Main Authors: Busby Jr, William F, Smith, Henrietta, Plummer, Elaine F, Lafleur, Arthur L, Mulder, Patrick P.J, Boere, Ben B, Cornelisse, Jan, Lugtenburg, Johan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 14-07-1997
• Subjects: Animals; Anthracenes - chemistry; Anthracenes - metabolism; Anthracenes - toxicity; Dose-Response Relationship, Drug; Ethylenes - chemistry; Fuel Oils; Methylation; Mitochondria, Liver - metabolism; Mutagenicity Tests; Mutagens - toxicity; Mutation; Polycyclic Aromatic Hydrocarbons - chemistry; Polycyclic Aromatic Hydrocarbons - metabolism; Polycyclic Aromatic Hydrocarbons - toxicity; Rats; Salmonella typhimurium - drug effects; Salmonella typhimurium - genetics; Salmonella typhimurium - metabolism; Structure-Activity Relationship; THCPAP, 4,5,6,7-tetrahydrocyclopent[ h,i]acephenanthrylene; DHAA, 1,2-dihydroaceanthrylene; PMS, Aroclor-induced rat liver postmitochondrial supernatant; AP, acephenanthrylene; CPAA, cyclopent[ h,i]aceanthrylene; 7-MeAP, 7-methylacephenanthrylene; 8-AG, 8-azaguanine; UCL, upper confidence limit; PAH, polynuclear aromatic hydrocarbons; 6-MeAA, 6-methylaceanthrylene; MDMC, minimum detectable mutagen concentration; THCPAA, 1,2,6,7-tetrahydrocyclopent[ h,i]aceanthrylene; CPAP, cyclopent[ h,i]acephenanthrylene; DHCPAP, 4,5-dihydrocyclopent[ h,i]acephenanthrylene; DMSO, dimethyl sulfoxide; AA, aceanthrylene
• ISSN: 1383-5718; 0027-5107; 1879-3592
• DOI: 10.1016/S0165-1218(97)00028-1

A series of cyclopenta-fused polynuclear aromatic hydrocarbons (PAH) were tested for mutagenicity in a bacterial forward mutation assay based on resistance to 8-azaguanine (8-AG) in
Salmonella typhimurium TM677 in the absence of Aroclor-induced rat liver postmitochondrial supernatant (PMS). All of the aceanthrylenes tested were mutagenic in the absence of PMS, whereas none of the acephenanthrylenes were active. The following mutagenic potency series expressed as the minimum detectable mutagen concentration (MDMC) in nmol/ml was obtained: aceanthrylene (AA) (5.5); cyclopent[
h,i]aceanthrylene (CPAA) (18.2); 6-methylaceanthrylene (6-MeAA) (112); 1,2,6,7-tetrahydrocyclopent[
h,i]aceanthrylene (THCPAA) (166); 1,2-dihydroaceanthrylene (DHAA) (298). Saturation of the cyclopenta rings or methylation at the 6-position of AA reduced, but did not eliminate, mutagenicity measured in the absence of PMS. AA was unusual because it was approximately 4-fold more mutagenic in the absence of PMS than in its presence. The other aceanthrylenes tested were 1.3–10.7 times more mutagenic in the presence of PMS than in its absence to give an MDMC potency series of: CPAA (3.8); 6-MeAA (10.5); AA (19.9); THCPAA (52.9); DHAA (229). Approximately 20% of the PMS-independent mutagenicity in a combustion sample from ethylene burned under fuel-rich conditions was found in a fraction containing only non-polar, 4–7 ring PAHs, widely attributed to be mutagenic only in the presence of PMS. None of this mutagenicity could be attributed to aceanthrylenes, thus other non-polar PAHs appear to possess significant PMS-independent mutagenicity as well.