Carcinogenesis, Vol. 20, No. 6, 1137-1141,
June 1999
© 1999 Oxford University Press
Short Communication |
Comparative tumorigenicity of the cyclopenta-fused polycyclic aromatic hydrocarbons aceanthrylene, dihydroaceanthrylene and acephenanthrylene in preweanling CD-1 and BLU:Ha mouse bioassays
1 Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205, USA,
2 Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA,
3 Leiden Institute of Chemistry, University of Leiden, 2300 RA Leiden, The Netherlands and
4 Gentest Corporation, Woburn, MA 01801, USA
Cyclopenta-fused polycyclic aromatic hydrocarbons are ubiquitous environmental pollutants and potential human health biohazards. In this study, the tumorigenicity of three single cyclopenta-fused polycyclic aromatic hydrocarbons, aceanthrylene, dihydroaceanthrylene and acephenanthrylene, was examined in preweanling CD-1 and BLU:Ha mouse bioassays at total doses of 175, 437.5 and 875 µg/mouse. No death or significant toxicity was observed with the treatment protocol in the tested animals. In CD-1 mice, a significant increase in lung tumor incidence (18–26%, P < 0.025–0.01) for these three compounds was recorded in animals treated with 875 µg as compared with the control animals (3%). Significant numbers of liver tumors (25–41%, P < 0.01–0.001) were induced in all aceanthrylene treatment groups and in animals treated with 875 µg acephenanthrylene (35%) at the termination at 9 months. Most liver tumors were induced in male animals. The ED50 values were estimated as 8.5, 10.6 and 12.8 µmol and the TM1.0 were 15.1, 20.4 and 23.1 µmol for aceanthrylene, acephenanthrylene and dihydroaceanthrylene, respectively. In BLU:Ha mice, there was a significant dose-dependent increase in lung tumor incidence, from 4% for the control group to 33% (P < 0.001) for the animals treated with 875 µg aceanthrylene and to 24% (P < 0.02) for the animals treated with 437.5 µg acephenanthrylene. The ED50 values were 6.0 and 4.4 µmol and the TM1.0 were 9.8 and 6.8 µmol for aceanthrylene and acephenanthrylene, respectively. No significant difference in lung tumor incidence between male and female mice was found. Based on these data and comparisons of tumorigenic potency with other polycyclic aromatic hydrocarbons previously tested in these newborn mouse bioassays, aceanthrylene and acephenanthrylene were classified as weak tumorigens.
Abbreviations: AA, aceanthrylene; AP, acephenanthrylene; BP, benzo[a]pyrene; CP-PAH, cyclopenta-fused polycyclic aromatic hydrocarbon; CPP, cyclopenta[c,d]pyrene; DHAA, 1,2-dihydroaceanthrylene; DMSO, dimethylsulfoxide; ED50, total dose inducing lung tumors in 50% of the treated mice; PAH, polycyclic aromatic hydrocarbon; PMS, post-mitochondrial supernatant; TM1.0, total dose inducing 1.0 lung tumor/mouse in treated mice.
5 To whom correspondence should be addressed at: Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, 615 North Wolfe Street, Room 1102, Baltimore, MD 21205, USA Email: jswang{at}jhsph.edu