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T Sofuni

Publications and source records attributed to T Sofuni.

At least 55 records · Page 3Linked to original sources
PubMed1998

DNA adduct level induced by 2-amino-3,4-dimethylimidazo[4,5-f]-quinoline in Big Blue mice does not correlate with mutagenicity.

In previous experiments we analyzed the mutant frequency (MF) and mutational types in various organs of lacI transgenic mice which were fed a diet containing 300 p.p.m. 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a food-borne mutagen/carcinogen. To clarify the relationships between mutational type and adduct molecular species and between adduct level and MF we analyzed adducts in the same DNA samples. The DNA adduct in the liver, heart, colon, forestomach and bone marrow was determined by the modified intensification method of 32P-post-labeling at time points 1, 4 and 12 weeks. Only a single spot corresponding to N2-(deoxyguanosin-8-yl)MeIQ 5'-monophosphate was detected in DNA from all organs at all time points examined, with a recovery of 48%. The difference in mutation type between bone marrow and other organs detected in the previous experiment was not explained by adduct molecular species. At 4 and 12 weeks administration the adduct levels were highest in the liver and then heart, colon, forestomach and bone marrow in decreasing order, with values of 28.3, 8.4, 3.3, 1.3 and 0.4 molecule/10(7) nucleotides at 12 weeks. Based on our previously reported data, lacI MF was highest in the colon and those in the liver, bone marrow and forestomach were 10-60% of that of the colon; no increase in MF was detected in the heart, where no DNA replication is expected except for vascular endothelial cells. There was no direct relationship between MF and adduct level. The MF may be the product of adduct level and cell proliferation rate.

Animals↗
PubMed1998

Specific mutational spectrum of dimethylnitrosamine in the lacI transgene of Big Blue C57BL/6 mice.

Dimethylnitrosamine (DMN) produces tumors in mice predominantly in the liver, but also in the kidney and lung. It forms O6-methylguanine adducts in DNA, which induce G:C-->A:T transitions. We have analyzed the spectra of spontaneous and DMN-induced mutations in the lacI transgene of the Big Blue mouse (C57BL/6). In both cases, mutations in the liver, kidney and lung were predominantly base substitutions, among which G:C-->A:T transitions were the most frequent. In contrast, a high incidence of short deletions (2-23 bp) was only found in the liver of treated mice. The deletions often occurred at direct repeat sequences. Single-base deletion incidence was also higher in the liver than in the kidney and lung. These results imply that accumulation of DNA lesions or their repair in liver is different from other organs. Spontaneous and induced base substitutions and deletions appeared to be randomly distributed in the lacI gene and an apparent hotspot was not observed, except for a 4 bp deletion of a (TGGC)3 sequence at positions 621-632. The present data demonstrate, for the first time, that DMN induces short deletions especially in the liver, although the mechanism involved needs further investigation.

Animals↗
PubMed1998

[Studies on development and improvement of toxicity guidelines conducted at the Biological Safety Research Center].

From FY 1990, studies aimed at development and improvement of toxicity guidelines have been conducted at the Biological Safety Research Center, in collaboration with the Environmental Health Bureau. To date, researches have focused on acute toxicity, antigenicity, reproductive toxicity, immunotoxicity, etc. In this report, brief summary of studies on cytotoxicity, toxicokinetics, neurotoxicity, genetic toxicity and structure-activity relationship performed during FY 1995-97, is presented.

Animals↗
PubMed1997

Multiple pathways for SOS-induced mutagenesis in Escherichia coli: an overexpression of dinB/dinP results in strongly enhancing mutagenesis in the absence of any exogenous treatment to damage DNA.

dinP is an Escherichia coli gene recently identified at 5.5 min of the genetic map, whose product shows a similarity in amino acid sequence to the E. coli UmuC protein involved in DNA damage-induced mutagenesis. In this paper we show that the gene is identical to dinB, an SOS gene previously localized near the lac locus at 8 min, the function of which was shown to be required for mutagenesis of nonirradiated lambda phage infecting UV-preirradiated bacterial cells (termed lambdaUTM for lambda untargeted mutagenesis). A newly constructed dinP null mutant exhibited the same defect for lambdaUTM as observed previously with a dinB::Mu mutant, and the defect was complemented by plasmids carrying dinP as the only intact bacterial gene. Furthermore, merely increasing the dinP gene expression, without UV irradiation or any other DNA-damaging treatment, resulted in a strong enhancement of mutagenesis in F'lac plasmids; at most, 800-fold increase in the G6-to-G5 change. The enhanced mutagenesis did not depend on recA, uvrA, or umuDC. Thus, our results establish that E. coli has at least two distinct pathways for SOS-induced mutagenesis: one dependent on umuDC and the other on dinB/P.

Bacterial Proteins↗
PubMed1997

A comparison of the genotoxicity of ethylnitrosourea and ethyl methanesulfonate in lacZ transgenic mice (Muta Mouse).

We compared the induction of gene mutations and chromosomal aberrations by ethylating agents in lacZ transgenic mice (Muta Mouse). Chromosomal aberrations were detected by the peripheral blood micronucleus assay. Gene mutations were detected in the lacZ transgene. A small amount of blood was sampled from a tail vessel during the expression time for fixation of gene mutations in vivo; this enabled us to detect and compare clastogenicity and gene mutations in the identical mouse. Single intraperitoneal injections of ENU (50-200 mg/kg) and EMS (100-400 mg/kg) strongly induced micronucleated reticulocytes (MN) detectable in peripheral blood 48 h after treatment. The maximum MN frequencies induced were 6.6% and 3.3% for ENU (100 mg/kg) and EMS (400 mg/kg), respectively (the control value was 0.3%). lacZ mutant frequency (MF) was analyzed in bone marrow and liver 7 days after treatment. Spontaneous MFs were 2.0-4.6 x 10(-6). MF in bone marrow was increased by ENU to 3.4 x 10(-5) at 200 mg/kg and induced by EMS to 1.8 x 10(-5) at 400 mg/kg. In liver, however, both chemicals at their highest doses induced only slight increases in MF. The induction of both micronuclei and lacZ mutations in bone marrow by both ENU and EMS correlated better with O6-ethylguanine adducts than with N7-ethylguanine adducts. The mutants (19 for ENU and 12 for EMS) were subjected to DNA sequence analysis. Among EMS-induced mutations, 75% were GC to AT transitions, which were probably caused by O6-ethylguanine. Among ENU-induced mutations, in contrast, 40% occurred as AT base pair substitutions (6 AT to TA transversions and 2 AT to GC transitions) (no such mutations were induced by EMS). These results, together with the known reactivity of ENU to thymine suggest that thymine adducts play a significant role in the ENU mutagenesis.

Animals↗
PubMed1997

New tester strains of Salmonella typhimurium lacking O6-methylguanine DNA methyltransferases and highly sensitive to mutagenic alkylating agents.

Salmonella typhimurium YG7104 and YG7108 are derivatives of the Ames tester strain TA1535, and have chromosomal deletions of the ogtST gene or both the ogtST and adaST genes, respectively. The ogtST and adaST genes encode O6-methylguanine DNA methyltransferases that are involved in the repair of DNA damage caused by alkylating agents. The sensitivities of these strains to 15 mutagens with different structures were tested and compared with those of the parent strain TA1535. Deletion of ogtST or ogtST plus adaST substantially increased the sensitivity of strain TA1535 to the mutagenicity of alkylating agents, such as N-ethyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate or dimethylnitrosamine (DMN). Preincubation of the chemical with S9 mix and bacteria for 20 min at 37 degrees C before pouring them together on agar plates was not necessary to detect the mutagenicity of DMN when strain YG7104 or YG7108 was used as a tester strain. Introduction of plasmid pKM101 did not enhance but rather decreased the sensitivity of YG7104 and YG7108 to alkylating agents. Since the new strains are highly sensitive only to alkylating agents, they will be useful to detect the mutagenicity with high efficiency and to study the mechanism of mutagenesis induced by environmental alkylating agents.

Alkylating Agents↗
PubMed1997

Construction of mutants of Salmonella typhimurium deficient in 8-hydroxyguanine DNA glycosylase and their sensitivities to oxidative mutagens and nitro compounds.

8-Hydroxyguanine (8-OH-G) DNA glycosylase is an enzyme involved in repair of oxidative DNA damage, e.g., 8-OH-G in DNA. In order to assess the roles of 8-OH-G in spontaneous and chemically-induced mutagenesis, the mutMST gene encoding 8-OH-G DNA glycosylase of Salmonella typhimurium was disrupted in several Ames tester strains, i.e., S. typhimurium TA1535 (hisG46, uvrB-, rfa), TA1975 (hisG46, uvr+, rfa) and TA102 (hisG428, uvr+, rfa). The spontaneous mutation frequencies were increased 2.4 and 1.6 times, respectively, by the mutMST deletions in strains TA1535 and TA1975, which are spontaneously reverted to His+ by mutations mainly at G:C base pairs. The resulting strains YG3001 (TA1535 delta mutMST) and YG3002 (TA1975 delta mutMST) were 2 to 8 times more sensitive to the mutagenicities of methylene blue plus visible light, neutral red plus visible light and 2-nitrofluorene than the parent strains. The strain YG3002 but not YG3001 was about 30 times more sensitive to the mutagenicity of 4-nitroquinoline N-oxide than the parent strain TA1975. Neither hydrogen peroxide nor phenazine methosulfate was mutagenic in the mutMST-deletion strains as well as in the parent strains. In contrast, the mutMST deletion did not affect the spontaneous mutation frequency of strain TA102, which has an A:T base pair at the critical site for reversion. The sensitivities of strain TA102 to the chemicals were not enhanced by the mutMST deletion except for hydrogen peroxide. These results suggest that 8-OH-G in DNA plays important roles in spontaneous mutagenesis occurring at G:C base pairs in S. typhimurium, and some nitro aromatics such as 4-nitroquinoline N-oxide or 2-nitrofluorene as well as the photosensitizers plus visible light can produce 8-OH-G in DNA, thereby inducing mutations. In the case of 4-nitroquinoline N-oxide, 8-OH-G rather than DNA adducts seems to play major roles in mutagenesis in uvr+ background. The new strains could be useful for the evaluation of the roles of 8-OH-G in mutagenesis in S. typhimurium and permit the efficient detection of some oxidative mutagens in the environment.

4-Nitroquinoline-1-oxide↗
PubMed1997

Detection of genotoxicity of polluted sea water using shellfish and the alkaline single-cell gel electrophoresis (SCE) assay: a preliminary study.

We exposed two species of shellfish, Patunopecten yessoensis and Tapes japonica, for 4 h to artificial sea water in which N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), ethyl nitrosourea (EMS), 3-chloro-4-dichloromethyl-5-hydroxy-2(H)-furanone (MX), or benzo[a]pyrene (B[a]P) were dissolved. We then assessed the DNA damage in cells isolated from the gills using the alkaline single-cell gel electrophoresis (SCG) assay. A statistically significant increase in DNA damage was observed for all exposures. Therefore, the alkaline SCG assay detected DNA damage in gill cells produced by direct mutagens and promutagen dissolved in sea water. T. japonica was exposed to sea water sampled from two Pacific Ocean coasts of Japanese local cities--Hachinohe (Aomori Prefecture, Tohoku) and Nakatsu (Oita Prefecture, Kyushu)--and three bay coasts of the industrial megalopolises--Tokyo, Osaka, and Kobe. A significant increase in DNA damage was observed after the exposure to sea water from Tokyo, Osaka, and Kobe, but not from Hachinohe and Nakatsu. These results suggested the utility of the alkaline SCG assay with shellfish gill cells for monitoring sea water genotoxicity.

Animals↗
PubMed1997

Extensive genetic heterogeneity in the neuroblastoma cell line NB(TU)1.

A neuroblastoma cell line displaying genetically unique features was established from a stage III case of a 20-month-old girl. Southern blotting by the probe pTNB6, which contains exon 1 of the N-myc gene, showed that the primary tumor had in total 4 aberrant bands beside the normal amplified band. The established cell line NB(TU)1 had an aberrant N-myc band (9.0 kb) in addition to the normal band (2.9 kb). Cytogenetic analysis revealed that NB(TU)1 has a composite karyotype composed of at least 7 related karyotypes, which are pseudo-diploid and contain complex chromosomal abnormalities, including translocations, deletions and homogeneously staining regions (HSRs). Such extensive abnormalities were considered to be prominent among known neuroblastoma cell lines, and it was suggested that NB(TU)1 had acquired a certain type of genetic instability. Analysis of N-myc bands in 11 clones of NB(TU)1 showed that the intensity ratio of the normal-sized band (2.9 kb) and the aberrant one (9.0 kb) markedly varied among clones. Moreover, 3 clones showed an additional band with the size of 3.7 kb, which was detectable neither in the parent NB(TU)1 nor in the primary tumor. Thus, NB(TU)1 was shown to be composed of heterogeneous cell components. To further detect such ongoing chromosomal instability, we examined micronuclei formation. NB(TU)1 yielded a larger number of micronuclei than 5 other neuroblastoma cell lines. We conclude that NB(TU)1 has acquired genetic instability detectable by both Southern blotting and cytogenetic analysis.

Abdominal Neoplasms↗
PubMed1997

Comparative study on organ-specificity of tumorigenicity, mutagenicity and cell proliferative activity induced by dimethylnitrosamine in Big Blue mice.

Recently, we have shown that dimethylnitrosamine (DMN) treatments increase lacI mutant frequency in the liver, kidney and lung but not in other organs, and also enhance cell proliferation only in the bronchial epithelia. In the present study, organ specificity of tumorigenicity induced by DMN was compared to those of lacI mutation and cell proliferation in Big Blue mice. Male 8-week-old Big Blue mice were treated with daily i.p. injections of 1 or 10 mg/kg DMN for 5 days, or a single i.p. injection of 5 or 10 mg/kg DMN. Except for the 10 mg/kg x 5 DMN group, all animals survived until 78 weeks after the first treatment of DMN. In the present study, the induction of cell proliferation in the bronchial epithelia was confirmed in a dose-dependent manner. At the termination of 78 weeks, it was histopathologically shown that the DMN-treated mice developed liver cell tumor in three out of seven (43%) of the 5 mg/kg group, renal tubule dysplasia in three out of seven (43%) of the 1 mg/kg x 5 group, and duodenal adenocarcinoma in one of seven (14%) of the 1 mg/kg x 5 group, although no neoplastic or preneoplastic lesions were found in the control mice. Because non-transgenic C57BL/6 mice are resistant to developing spontaneous liver cell and duodenal tumors, it was speculated that even these low doses of DMN could be sufficient to initiate target cells. Our results thus suggest that organ specificity of tumorigenicity by DMN is in favorable agreement with that of lacI mutation but not with possibly temporal cell proliferation induced by DMN.

Animals↗
PubMed1997

Targeted disruption of the gene encoding the classical nitroreductase enzyme in Salmonella typhimurium Ames test strains TA1535 and TA1538.

The gene encoding the 'classical nitroreductase' (CNR) of Salmonella typhimurium was disrupted. In this manner, cnr null mutant derivatives of strains TA1535 and TA1538 were constructed, and named YG7131 and YG7127, respectively. In both strain backgrounds, cnr gene disruption reduced nitrofurazone-reductase activity. This reduction almost completely eliminated the nitroreductase activity of strain TA1538. In contrast, the nitroreductase activity of strain TA1535 was much higher than that in TA1538. In this background, cnr gene disruption resulted in a reduction in nitroreductase activity by a similar absolute amount as in TA1538, but representing only about one-quarter of the original activity of TA1535. The results suggest that S. typhimurium has originally at least two distinct nitroreductases, one of which is already deficient in strain TA1538; the CNR is present in both TA1535 and TA1538. Also, these two strains (including their derivatives, TA98 and TA100) are not isogenic with regard to nitroreductase activity. After the introduction of plasmid pKM101, the sensitivities of the strains YG7132 and YG7128, the cnr-null mutants of TA98 and TA100, respectively, against several nitro compounds were compared with those of the conventional cnr-deficient strains TA98NR and TA100NR and the wild-type strains TA98 and TA100. The mutagenicities of 2-nitrofluorene and 1-nitropyrene in YG7132 or TA98NR were ten-fold lower than those of the compounds in TA98. Similarly, the mutagenicity of 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide in strain YG7128 or TA100NR was substantially lower than that of the compound in TA100. However, the mutagenicity of 2-nitronaphthalene in YG7128 was between those observed with TA100 and TA100NR, suggesting that a nitroreductase in S. typhimurium other than CNR is involved in the metabolic activation of this compound. The cnr gene of S. typhimurium positively hybridized with DNA at 13 min on the E. coli chromosome where the nfsB and nfnB genes of E. coli are mapped. These results suggest that the cnr gene of S. typhimurium is a counterpart of the nfsB and nfnB genes of E. coli, and that the newly constructed cnr-deletion strains are useful to assess the role of nitroreductases in the metabolic activation of mutagenic nitro compounds.

Blotting, Southern↗
PubMed1997

Chlorambucil-induced structural changes in the gpt gene of AS52 cells.

The bifunctional alkylating agent chlorambucil (CBC) is a chemotherapeutic agent that induces a high yield of mouse germ-line mutations, apparently due to multi-locus deletions or other chromosomal rearrangements. We investigated the mutagenicity of CBC in cultured mammalian cells by comparing its effect in the AS52/gpt and CHO/hprt gene mutation assays, which detect large and small effects, respectively. CBC significantly increased the mutant frequency in the AS52/gpt assay, but not in the CHO/hprt assay, while the cytotoxic responses to CBC were similar in the two cell lines. This indicates that CBC induced predominantly large deletions or other gross structural changes, and not point or other small mutations. The mutational responses to CBC were similar to the responses to mitomycin C comparing them based on the cytotoxic responses. Molecular analysis of the gpt gene in AS52 mutant cells by electrophoresis following PCR amplification revealed that 81% of CBC-induced mutants lost the entire gpt gene, which is caused by large deletions or interchromosomal recombinations. The loss frequency was lower in spontaneous mutants (42%) and ethylmethanesulfonate-induced mutants (29%). This supports cytogenetic data showing that CBC is a potent clastogen in cultured mammalian cells, inducing predominantly large deletions and/or other gross structural alterations.

Animals↗
PubMed1997

Cytotoxic and mutagenic responses to X-rays and chemical mutagens in normal and p53-mutated human lymphoblastoid cells.

To investigate the role of p53 as a guardian of the genome, the mutagenic and cytotoxic responses to mutagens were compared for normal (TK6) and p53-mutated (WTK-1) cells. The characteristics of the mutations that occurred in these cells was also examined. Human lymphoblastoid cell lines TK6 and WTK-1 are derived from the same progenitor cell line, but WTK-1 cells have homozygous p53 mutations resulting in overproduction of mutant p53 protein. The spontaneous mutation frequency at the heterozygous thymidine kinase (tk) locus in TK6 and WTK-1 cells was 3.5 X 10(-6) and 101.1 X 10(-6), respectively. WTK-1 cells were more resistant than TK6 cells to cytotoxic damage by X-rays, ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS), and were more sensitive at the tk locus to the mutagenic effects of X-rays, EMS, MMS and mitomycin C. Molecular analysis of TK mutants by Southern-hybridization demonstrated that 70% of spontaneous mutations and 86% of X-ray induced mutations in TK6 cells resulted from loss of the entire tk allele (loss of heterozygosity; LOH), while 95% of spontaneous and 100% of X-ray induced mutations showed LOH in WTK-1 cells. Densimetric analysis revealed that almost all of the LOH mutants in WTK-1 cells were homozygous at the tk locus, consistent with inter-allelic homologous recombination, or gene conversion. These data indicate that p53-mutated WTK-1 cells are hypermutable, susceptible to some environmental mutagens, and prone to LOH-type gene mutations because of their abnormally high recombinational activity. It may be that genetic instability in p53-mutated cells significantly contribute to the subsequent occurrence of LOH mutations during a multistep tumorigenic process.

Cell Line↗
PubMed1997

Evaluation of the rodent micronucleus assay in the screening of IARC carcinogens (groups 1, 2A and 2B) the summary report of the 6th collaborative study by CSGMT/JEMS MMS. Collaborative Study of the Micronucleus Group Test. Mammalian Mutagenicity Study Group.

To assess the correlation between micronucleus induction and human carcinogenicity, the rodent micronucleus assay was performed on known and potential human carcinogens in the 6th MMS/CSGMT collaborative study. Approximately 100 commercially available chemicals and chemical groups on which there was little or no micronucleus assay data were selected from IARC (International Agency for Research on Cancer) Groups 1 (human carcinogen), 2A (probable human carcinogen) and 2B (possible human carcinogen). As minimum requirements for the collaborative study, 5 male mice were treated by intraperitoneal injection or oral gavage once or twice with each chemical at three dose levels, and bone marrow and/or peripheral blood was analyzed. Five positives and 2 inconclusives out of 13 Group 1 chemicals, 7 positives and 5 inconclusives of 23 Group 2A chemicals, and 26 positives and 6 inconclusives of 67 Group 2B chemicals were found. Such low positive rates were not surprising because of a test chemical selection bias, and we excluded well-known micronucleus inducers. The overall evaluation of the rodent micronucleus assay was based on the present data combined with published data on the IARC carcinogens. After merging, the positive rates for Groups 1, 2A and 2B were 68.6, 54.5 and 45.6%, respectively. Structure-activity relationship analysis suggested that the micronucleus assay is more sensitive to the genetic toxicity of some classes of chemicals. Those to which it is sensitive consist of (1) aziridines and bis(2-chloroethyl) compounds; (2) alkyl sulfonate and sulfates; (3) acyl-type N-nitroso compounds; (4) hydrazines; (5) aminobiphenyl and benzidine derivatives; and (6) azo compounds. Those to which it is less sensitive consist of (1) dialkyl type N-nitroso compounds; (2) silica and metals and their compounds; (3) aromatic amines without other functional groups; (4) halogenated compounds; and (5) steroids and other hormones. After incorporation of structure-activity relationship information, the positive rates of the rodent micronucleus assay became 90.5, 65.2 and 60.0% for IARC Groups 1, 2A and 2B, respectively. Noteworthy was the tendency of the test to be more sensitive to those carcinogens with stronger evidence human carcinogenicity.

Animals↗
PubMed1997

Ethyl nitrosourea and methyl methanesulfonate mutagenicity in sperm and testicular germ cells of lacZ transgenic mice (Muta Mouse).

The germ cell mutagens ethyl nitrosourea (ENU) and methyl methanesulfonate (MMS), were tested for their genotoxicity in sperm cells and testicular germ cells using lacZ transgenic mice (Muta Mouse). Eight- to 10-week-old Muta mice were treated with ENU (150 mg/kg) or MMS (40 mg/kg) by intraperitoneal injection. Three and 14 days after treatment, testes and sperm were collected for lacZ mutation analysis. Sperm were isolated from the epididymis and vas deferens by washing out the minced tissue. Germ cell DNA was isolated from testicular germ cells and sperm with the help of 2-mercaptoethanol, and the target lacZ gene, which is integrated into a lambda shuttle vector, was recovered by in vitro packaging. The resultant phages were allowed to infect to E. coli C (galE), and the lacZ mutant plaques were dominantly selected on a plate containing phenyl-beta-D-galactoside. Spontaneous mutant frequencies (MF) in vehicle-treated control mice were approximately 1 x 10(-5) and 3 x 10(-5) in testicular germ cells and sperm, respectively, at both sampling times. ENU treatment increased the MF in the testicular germ cells to 5 x 10(-5) on days 3 and 14, but did not affect sperm MF. MMS was not mutagenic in either tissue. The peripheral blood micronucleus assay was performed on the same animals 48 h after treatment, and strong inductions of micronucleated reticulocytes (MNRETs) were observed in both ENU- and MMS-treated mice. These data suggest that agents mutagenic to premeiotic germ cells, e.g., ENU, can be detected by transgenic mutation assay system using germ cells isolated from the testis. On the other hand, those mutagenic to postmeiotic cells, e.g., MMS, are insensitive in the assay system.

Animals↗
PubMed1997

Increased sensitivity of scid heterozygous mice to ionizing radiation.

In the present study, acute effects of ionizing radiation on animal survival, bone marrow cells and fibroblast cell lines of scid homozygous, scid heterozygous and wild-type mice with the same C.B-17 genetic background were examined. The sensitivities to ultraviolet light (UV) and various chemicals, bleomycin, mitomycin C, N-methyl-N'-nitro-N-nitrosoguanidine, methyl methanosulphonate, 5-fluorouracil, 6-mercaptopurine, 4-nitroquinoline 1-oxide and potassium bromate) were also investigated. In addition, micronucleus testing of whole-body irradiated mice was performed. Scid heterozygous mice were found to be less sensitive than the homozygotes but more sensitive to ionizing radiation than wild-type mice, not only in vivo but also for bone marrow cells in vitro, suggesting partial dominance under both conditions. In contrast, there were no differences in sensitivity to UV light and various chemicals, as compared with wild-type and scid heterozygous cell lines, either in vitro or in the micronucleus test.

Animals↗