Multiple organ mutation in the lacZ transgenic mouse (Muta (TM) Mouse) 6 months after oral treatment (5 days) with benzo[a]pyrene

We have recently demonstrated that not all organs with high rates of mutati on in the lacZ transgene develop tumors using the Muta(TM) Mouse. To better understand the role of in vivo mutation in carcinogenesis, we examined the mutant frequencies (IMF) of the lacZ transgene in tumor-bearing and non tu mor-bearing organs. MF, recovered after 2 weeks (the data taken from our pr evious study) and after 26 weeks following oral doses of 125 mg kg(-1) day( -1) benzo[a]pyrene (BP) for five days were compared. The organs examined in cluded the target organs (forestomach, spleen, and lung) and non-target org ans (colon, glandular stomach, and liver) for BP carcinogenesis, The data i ndicated that lacZ MF were markedly increased over spontaneous frequencies in the organs examined and that the organ which showed the highest MF was t he colon, followed by the forestomach > spleen > glandular stomach, liver, and lung in that order. These findings indicate that the MF of the lacZ tra nsgene in each organ, even 26 weeks after the start of the treatment does n ot fully correlate with the known target organs of BP. Furthermore, the lac Z MF in a non-papilloma region of a forestomach with a papilloma was equiva lent to the two highest MF observed in the healthy colon (non-target organ) of mice at 26 weeks, These observations also indicate that the generation of tumors requires the induction of mutations as well as other factor(s) sp ecific to the target organs. These results clearly suggest that highly muta ted organs do not always progress to tumors in the transgenic mouse. (C) 19 99 Elsevier Science B.V. All rights reserved.