Mammary tumorigenesis enhanced by carcinogen exposures in iWnt mice. (A) Rapid onset of mammary tumors in carcinogen-exposed iWnt mice. One week after starting Dox treatment, cohorts of iWnt mice were left unexposed (Dox only, n = 18) or subjected to one-time exposure to either DMBA (n = 6) or ENU (n = 4), then monitored for mammary tumors. Tumor onset was more rapid in carcinogen-exposed versus unexposed cohorts (P < 0.0001, log rank test). (B) Increased tumor multiplicity following carcinogen exposure. Nearly all iWnt mice developed solitary mammary tumors in the absence of carcinogen exposure, whereas carcinogen-exposed mice developed numerous mammary tumors synchronously. Error bars depict standard error of the mean. *Denotes P < 0.0001, t-test. (C) Uniform iWnt mammary tumor histopathology in the presence and absence of carcinogen exposure. Tumors were mixed-lineage adenocarcinomas with prominent tumor cell nests and intervening stroma. Scale bar, 50 µm.