Reference SummaryPrahalad AK, Carcinogenesis 1997 Oct;18(10):1955-63

Title	Dibenzo[a,l]pyrene-induced DNA adduction, tumorigenicity, and Ki-ras oncogene mutations in strain A/J mouse lung.
Authors	Prahalad AK; Ross JA; Nelson GB; Roop BC; King LC; Nesnow S ; Mass MJ
Journal	Carcinogenesis
Volume	18
Issue	10
Year	1997
Pages	1955-63
Abstract	Dibenzo[a,l]pyrene (DB[a,l]P), an environmental polycyclic aromatic hydrocarbon, is the most potent carcinogen ever tested in mouse skin and rat mammary gland. In this study, DB[a,l]P was examined for DNA adduction, tumorigenicity, and induction of Ki-ras oncogene mutations in tumor DNA in strain A/J mouse lung. Groups of mice received a single i.p. Injection of 0.3, 1.5, 3.0, or 6.0 mg/kg DB[a,l]P in tricaprylin. Following treatment, DNA adducts were measured at times between 1 and 28 days, while tumors were counted at 250 days and analyzed for the occurrence of point mutations in codons 12 and 61 of the Ki-ras oncogene. DB[a,l]P in strain A/J mouse lung induced six major and four minor DNA adducts. Maximal levels of adduction occurred between 5 and 10 days after injection followed by a gradual decrease. DB[a,l]P-DNA adducts in lung tissue were derived from both anti- and syn-11,12- dihydroxy-13,14-epoxy-11,12,13,14- tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) and both deoxyadenosine (dAdo) and deoxyguanosine (dGuo) residues in DNA as revealed by cochromatography The major adduct was identified as a product of the reaction of an anti- DB[a,l]PDE with dAdo in DNA. DB[a,l]P induced significant numbers of lung adenomas in a dose-dependent manner, with the highest dose (6.0 mg/kg) yielding 16.1 adenomas/mouse. In tricaprylin-treated control animals, there were 0.67 adenomas/mouse. Based on the administered dose, DB[a,l]P was more active than other environmental carcinogens including benzo[a]pyrene. As a function of time-integrated DNA adduct levels, DB[a,l]P induced lung adenomas with about the same potency as other PAHs, suggesting that the adducts formed by DB[a,l]P are similar in carcinogenic potency to other PAHs in the strain A/J mouse lung model. Analysis of the Ki-ras mutation spectrum in DB[a,l]P- induced lung tumors revealed the predominant mutations to be G-->T transversions in the first base of codon 12, A-- >G transitions in the second base of codon 12, and A-->T transversions in the second or third base of codon 61, concordant with the DNA adduct profile.
Links	J:44141 – MGI References 9364006 – National Library of Medicine/PubMed

Models
Strain	Model Name	Treatment Agent(s)	Organ Affected	Frequency	Model Details
A/J	Lung adenoma	tricaprylin (trioctanoin)	Lung	50
A/J	Lung adenoma	dibenzo[a,l]pyrene (DB[a,l]P)	Lung	43 - 100
A/J	Lung adenoma	urethane (ethyl carbamate)	Lung	100
A/J	Lung adenoma	benzo[a]pyrene (BP) (BaP) (B[a]P)	Lung	observed
A/J	Lung adenoma	benzo[b]fluoranthene (B[b]F)	Lung	observed
A/J	Lung adenoma	cyclopental[c,d]pyrene (CPP)	Lung	observed
A/J	Lung adenoma	5-methylchrysene (5-MeC)	Lung	observed
A/J	Lung adenoma		Lung	50