Induction of preneoplastic lesions by sequential treatment of rats with three carcinogens: N-butyl-N-(4-hydroxybutyl) nitrosamine, 7,12-dimethylbenz(a)-anthracene, and N-methyl-N-nitro-N-nitrosoguanidine.

Abstract

N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), 7, 12-dimethylbenz(a)anthracene (DMBA), and N-methyl-N-nitro-N-nitrosoguanidine (MNNG) were given by gastric intubation, in sequence, to 6-week-old female SD rats. After receiving BBN (600mg/kg body wt.) three times, every other day, in the 1st week, the animals were administered a single dose of DMBA (50mg/kg body wt.) at the beginning of week 2 and MNNG (100mg/kg body wt.) three times every other day in the 3rd week. Groups were sacrificed at the end of weeks 12, 16, 20, and 24 of the experiment. The putative preneoplas-tic lesion, papillary or nodular hyperplasia as well as papillomas were found in the urinary bladder after week 16 but the incidences were very low. Adenocarcinoma in the mammary gland appeared after week 12 at a high incidence. Papilloma and carcinoma in the forestomach were induced after week 16. Pepsinogen isoenzyme 1 altered pyloric glands could be detected immunohistochemically after week 12. These results indicate that treatment with the three carcinogens given in sequence is effective for induction of preneoplastic and neoplastic lesions in the urinary bladder, mammary gland, forestomach, and glandular stomach of rats in a relative short-period.