| First Author | Nesnow S | Year | 1995 |
| Journal | Toxicology | Volume | 105 |
| Issue | 2-3 | Pages | 403-13 |
| PubMed ID | 8571376 | Mgi Jnum | J:32177 |
| Mgi Id | MGI:79682 | Doi | 10.1016/0300-483x(95)03238-b |
| Citation | Nesnow S, et al. (1995) Mechanistic linkage between DNA adducts, mutations in oncogenes and tumorigenesis of carcinogenic environmental polycyclic aromatic hydrocarbons in strain A/J mice. Toxicology 105(2-3):403-13 |
| abstractText | Five polycyclic aromatic hydrocarbons (PAHs), benzo[a]pyrene (B[a]P), benzo[b]fluoranthene (B[b]F), dibenz[a,h]anthracene (DBA), 5-methylchyrsene (5MC), and cyclopenta[cd]pyrene (CPP) were examined for their lung tumorigenic activities in strain A/J mice, their ability to form PAH-DNA adducts in lung tissues, and their ability to mutate the Ki-ras oncogene in PAH-induced tumors. PAHs dissolved in tricapyrlin were administered by single intraperitoneal injection to male strain A/J mice (20 mice/dose) at doses up to 200 mg/kg depending on the PAH. Animals were sacrificed 8 months later and the lungs removed, fixed, and surface adenomas enumerated. DBA produced maximal tumor multiplicity at the highest dose, 10 mg/kg, giving 32.2 lung adenomas per mouse. At 100 mg/kg, B[a]P, B[b]F, 5MC, and CPP gave 12.8, 5.3, 93.1, and 32.2 lung adenomas per mouse, respectively. The dose response data for each PAH was fit to y = 0.6 + bx1.6, where y is the observed mean lung adenomas per mouse at dose x (in mg/kg), 0.6 is the observed background of lung adenomas per mouse, and b is the fitted constant representing the potency of each PAH. Statistical analysis indicated that the fit of the data to the equation was extremely high with adjusted R2 values > 0.985 and small fit standard errors. Based on this equation, the relative potencies of B[b]F, DBA, 5MC, and CPP compared to B[a]P were PAH (relative activity): DBA (118); 5MC (8.8); CPP (2.9); B[a]P (1.0); B[b]F (0.43). DNA adducts were measured by 32P-postlabeling techniques on DNA from lungs of mice treated with these PAHs. Adducts identified by cochromatography with standards were: from B[a]P, 7R,8S,9S-trihydroxy-10R-(N2-2'-deoxyguanosyl)-7,8,9,10-tetrahydro- |
