Comparison between in vivo mutagenicity and carcinogenicity in multiple organs by benzo[a]pyrene in the lacZ transgenic mouse (Muta Mouse).
To evaluate whether the in vivo mutagenicity test system using the lacZ transgenic mice (Muta Mouse) may be applied to carcinogenesis studies, both the in vivo mutagenicity and carcinogenicity of benzo[a]pyrene (BP) was tested in mice under the same administration conditions. The eleven organs of the mice on the 14th day after the final oral administration of BP at a dose of 125 mg kg(-1) day(-1) or corn oil for 5 consecutive days were tested for in vivo mutation by the positive-selection method. The data show that the colon had the highest lacZ mutant frequency (37-fold increase over the spontaneous frequency), followed by the ileum > forestomach > bone marrow, spleen > glandular stomach > liver, lung > kidney and heart. No significant mutations were found in the brain. These results may suggest that, in general, the organs with rapidly proliferative tissues have a marked increase in vivo mutant frequencies under the conditions of this experimental design. The forestomach and lymphatic organs including the spleen (malignant lymphoma) were the main target organs for BP carcinogenesis by 5 daily oral doses of 75 and 125 mg kg(-1) day(-1). These results suggest that the mutation results from the transgenic assay with BP reflect the carcinogenicity of BP in the mouse. They also indicate, however, that the magnitude of the in vivo lacZ mutant frequencies induced by BP in different organs did not fully correlate with the target organs for carcinogenicity.
Hakura
A
A
Drug Safety Research Laboratories, Ibaraki, Japan. al-hakura@eisai.co.jp
Tsutsui
Y
Y
Sonoda
J
J
Kai
J
J
Imade
T
T
Shimada
M
M
Sugihara
Y
Y
Mikami
T
T
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D007763:Lac Operon / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009153:Mutagens / Q000633:toxicity*; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology
D002273:Carcinogens; D009153:Mutagens; D001564:Benzo(a)pyrene