- Email: [email protected]
Induction of the SOS responses by 5-fluorouracil in Escherichia coli
270
Oncogene of sarcomas induced by 1,8-dinitropyrene in rats 1,8-Dinitropyrene (1,8-DNP) is an extremely potent environmental mutagen in Salmonella typhimurium TA98 and TA100 without $9 mix. 1,8-DNP also showed strong mutagenicity to Chinese hamster lung cells without $9 mix, using diphtheria toxin resistance as a marker. When a total dose of 4 mg of 1,8-DNP was injected subcutaneously into F344 male rats, sarcomas were induced in all the rats. High molecular weight DNAs were extracted from 7 primary sarcomas and first transplant. DNAs were transfected into NIH3T3 cells by the calcium phosphate coprecipitation procedure. DNAs of 9 primary transformants were analyzed by Southern blot hybridization. One of them contained rat Ki-ras gene, in addition to mouse c-Kiras. DNAs of all 7 secondary transformants induced by DNA of one primary transformant contained rat c-Ki-ras, c-Ki-ras in the original sarcomas was not rearranged. Cloning of c-Ki-ras in normal rat liver and in the primary transformant in which c-Ki-ras was activated is in progress.
41 Oda, Y., K. Yamamoto, S. Nakamura and I. Oki, Osaka Prefectural Institute of Public Health, Nakamichi-1, Higashinari-ku, Osaka 537 (Japan) Induction of the S O S responses by 5-fluorouracil in Escherichia coli 5-Fluorouracil (5-FU) is one of the pyrimidine analogues used clinically in the treatment of several human neoplasms. In order to understand the molecular mechanisms of 5-FU, we investigated the induction of umu operon expression, cell killing and induction of W-reactivation of UV-irradiated phage by 5-FU in Escherichia coli K12 strains with special references to the effects of SOS-repair deficiencies. (1) The expression of umu operon was inducible by 5-FU and the induction was regulated by the lexA and recA genes. (2) The lexA, recA and uvrA mutant strains were as sensi-
tive as the wild-type strain to the lethal effect of 5-FU. (3) The plating efficiency of UV-irradiated phage was increased by 5-FU treatment of the wild-type host cell (W-reactivation). This increase was not observed in the lexA and recA mutant hosts. It has been shown that 5-FU induces prophage (Marcovich and Kaplan, 1963). Thus, 5-FU induces a set of SOS functions including those related to DNA repair and mutagenesis.
42 Odagiri, Y., S. Adachi and K. Takemoto, Saitama Medical School, Saitama (Japan) Detection of cytogenetic effect of inhaled aerosols by the mieronucleus test The induction of micronuclei in mice exposed to aerosols of the following 6 chemicals was examined: cyclophosphamide, methyl methanesulfonate, mitomycin C, dimethylnitrosamine, ethylcarbamate and colchicine. The aerosol was generated by atomizing a solution of each chemical with an ultrasonic nebulizer. Control mice were exposed to the aerosol of saline or distilled water for 30 min. Exposure of mice to cyclophosphamide aerosol (2660 m g / m 3) for 29, 81 and 139 min induced 0.58, 1.00 and 2.32% of micronucleated polychromatic erythrocytes, respectively. The similar exposure/response relationships were also observed in the other chemicals except for dimethylnitrosamine. Dimethylnitrosamine showed only a weak activity even when high doses were used. The results obtained in this study suggest that the micronucleus test is now available for detecting the cytogenetic effect of inhaled aerosols.
43 Ohnishi, Y., T. Kinouchi and H. Tsutsui, Department of Bacteriology, School of Medicine, The University of Tokushima, Tokushima 770 (Japan) Mutagenicity and nitropyrene content in indoor air heated with a kerosene heater
Oncogene of sarcomas induced by 1,8-dinitropyrene in rats 1,8-Dinitropyrene (1,8-DNP) is an extremely potent environmental mutagen in Salmonella typhimurium TA98 and TA100 without $9 mix. 1,8-DNP also showed strong mutagenicity to Chinese hamster lung cells without $9 mix, using diphtheria toxin resistance as a marker. When a total dose of 4 mg of 1,8-DNP was injected subcutaneously into F344 male rats, sarcomas were induced in all the rats. High molecular weight DNAs were extracted from 7 primary sarcomas and first transplant. DNAs were transfected into NIH3T3 cells by the calcium phosphate coprecipitation procedure. DNAs of 9 primary transformants were analyzed by Southern blot hybridization. One of them contained rat Ki-ras gene, in addition to mouse c-Kiras. DNAs of all 7 secondary transformants induced by DNA of one primary transformant contained rat c-Ki-ras, c-Ki-ras in the original sarcomas was not rearranged. Cloning of c-Ki-ras in normal rat liver and in the primary transformant in which c-Ki-ras was activated is in progress.
41 Oda, Y., K. Yamamoto, S. Nakamura and I. Oki, Osaka Prefectural Institute of Public Health, Nakamichi-1, Higashinari-ku, Osaka 537 (Japan) Induction of the S O S responses by 5-fluorouracil in Escherichia coli 5-Fluorouracil (5-FU) is one of the pyrimidine analogues used clinically in the treatment of several human neoplasms. In order to understand the molecular mechanisms of 5-FU, we investigated the induction of umu operon expression, cell killing and induction of W-reactivation of UV-irradiated phage by 5-FU in Escherichia coli K12 strains with special references to the effects of SOS-repair deficiencies. (1) The expression of umu operon was inducible by 5-FU and the induction was regulated by the lexA and recA genes. (2) The lexA, recA and uvrA mutant strains were as sensi-
tive as the wild-type strain to the lethal effect of 5-FU. (3) The plating efficiency of UV-irradiated phage was increased by 5-FU treatment of the wild-type host cell (W-reactivation). This increase was not observed in the lexA and recA mutant hosts. It has been shown that 5-FU induces prophage (Marcovich and Kaplan, 1963). Thus, 5-FU induces a set of SOS functions including those related to DNA repair and mutagenesis.
42 Odagiri, Y., S. Adachi and K. Takemoto, Saitama Medical School, Saitama (Japan) Detection of cytogenetic effect of inhaled aerosols by the mieronucleus test The induction of micronuclei in mice exposed to aerosols of the following 6 chemicals was examined: cyclophosphamide, methyl methanesulfonate, mitomycin C, dimethylnitrosamine, ethylcarbamate and colchicine. The aerosol was generated by atomizing a solution of each chemical with an ultrasonic nebulizer. Control mice were exposed to the aerosol of saline or distilled water for 30 min. Exposure of mice to cyclophosphamide aerosol (2660 m g / m 3) for 29, 81 and 139 min induced 0.58, 1.00 and 2.32% of micronucleated polychromatic erythrocytes, respectively. The similar exposure/response relationships were also observed in the other chemicals except for dimethylnitrosamine. Dimethylnitrosamine showed only a weak activity even when high doses were used. The results obtained in this study suggest that the micronucleus test is now available for detecting the cytogenetic effect of inhaled aerosols.
43 Ohnishi, Y., T. Kinouchi and H. Tsutsui, Department of Bacteriology, School of Medicine, The University of Tokushima, Tokushima 770 (Japan) Mutagenicity and nitropyrene content in indoor air heated with a kerosene heater