Dose-response relationships of the tumorigenicity of cyclopenta[cd]pyrene, benzo[a]pyrene and 6-nitrochrysene in a newborn mouse lung adenoma bioassay.
Cyclopenta[cd]pyrene (CPP) was a potent tumorigen when tested over a 5-fold dose range in the newborn mouse assay. A 20-fold increase in lung tumor multiplicity and a nearly 8-fold increase in tumor incidence was observed at the lowest total dose tested (1.55 mumol) with the dose-response relationship indicating a saturation of tumor multiplicity at approximately 7 tumors/animal. No liver nodules or lymphatic system tumors were noted. Analysis of dose-response data for benzo[a]-pyrene (BaP) and 6-nitrochrysene (6-NC) showed that tumor multiplicity for BaP also saturated at approximately 7 tumors/animal, whereas no similar saturation was found for 6-NC at up to 40 tumors/animal. Progression of lung adenomas to adenocarcinomas, as measured by the incidence of mice bearing malignant tumors, was essentially a linear function of dose. To facilitate comparison and maximize quantitative data obtainable from the newborn mouse assay-parameters were defined for tumor incidence (ED50), tumor multiplicity (TM1.0) and tumor malignancy (malignancy index). Values for the ED50 and TM1.0 were similar for the same compound and a tumorigenic potency series of 6-NC greater than BaP greater than CPP was obtained corresponding to a ratio of approximately 1:10-25:76.5-135, respectively. The malignancy index, however, indicated increased adenocarcinoma induction in the order CPP greater than 6-NC greater than BaP as expressed by the ratio 1:1.4:8.3, respectively.
Busby
W F
WF
Department of Applied Biological Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Stevens
E K
EK
Kellenbach
E R
ER
Cornelisse
J
J
Lugtenburg
J
J
D000236:Adenoma / Q000139:chemically induced*; D000818:Animals; D000831:Animals, Newborn; D001564:Benzo(a)pyrene; D001681:Biological Assay / Q000379:methods*; D002273:Carcinogens; D002911:Chrysenes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010616:Phenanthrenes / Q000633:toxicity*; D011721:Pyrenes / Q000633:toxicity*; D012878:Skin Neoplasms / Q000139:chemically induced
D002273:Carcinogens; D002911:Chrysenes; D010616:Phenanthrenes; D011721:Pyrenes; C016328:cyclopenta(c,d)pyrene; D001564:Benzo(a)pyrene; C035986:6-nitrochrysene