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PubMed1998

Mutation spectrum and phenylalanine hydroxylase RFLP/VNTR background in 44 Romanian phenylketonuric alleles.

The mutation spectrum and polymorphic haplotype background in 22 Romanian families have been analysed in this study using the restriction digestion of phenylalanine hydroxylase (PAH) regions specifically amplified or the DGGE/direct sequencing methods. Eleven PAH mutations specifically associated with six mutant haplotypes were detected. In spite of the relative heterogeneity of the molecular defects in the PAH gene, three mutations covered almost 70% of all alleles: R408W, 47.72%, 21/44; K363fsdelG 13.63%, 6/44; and P225T 6.81%, 3/44. Among these, R408W, the most frequent mutation in our population, represented 50% of all the phenylketonuric (PKU) chromosomes. Splice mutation IVS12nt1g-->a affected two PAH alleles (4.54%); the remaining seven mutations were rare, each having an effect on just one chromosome (1/44), resulting in a relative frequency of 2.27%. A high frequency was observed in our PKU samples for the relatively uncommon mutations, K363fsdelG and P225T mutation, suggesting a possible founder effect at origin. Within the investigated panel, these mutations, both very rare among other Caucasians were exclusively linked to haplotype 5.8 and 1.7, respectively. These results provide a basis for the development of a routine molecular analysis of Romanian PKU families.

Adult↗

PubMed1981

[Ratio of the mutation spectrum to the physiological state of the Penicillium chrysogenum cell. Auxotrophic mutations induced by UV rays at different stages of DNA replication].

The spectrum of the mutations obtained with exposure of nonactivated spores of Pen. chrysogenum to N-nitrozo-N-methylbiuret (NMB) was studied and it was shown that the mutations associated with blocking of amino acid synthesis predominated. When activated spores of Pen. chrysogenum were treated with the mutagen, correlation was observed between the spectrum of the induced mutations, the physiological state of the cells and the exposure time. It is supposed that the mutagen molecule affects the replicating part of the DNA molecule. Schemes for predominating liberation of the mutations according to the markers in time were developed. This may give an idea of the order of the markers in genome.

DNA Replication↗

PubMed1996

p53 mutational spectrum of esophageal carcinomas from five different geographical locales in China.

A mutational spectrum for exons 5-8 of the p53 tumor suppressor gene in esophageal carcinomas in mainland China and Hong Kong was established. This study involved 209 squamous cell carcinoma specimens obtained from five different geographical locales in China: Zhengzhou, Taiyuan, Shantou, Guangzhou, and Hong Kong. Zhengzhou and Shantou were high-incidence regions for esophageal cancer, whereas the other three regions had low or intermediate incidence of the disease. Analysis by single-strand conformation polymorphism and DNA sequencing showed that 87 specimens (41.6%) contained mutations in exons 5-8 of the p53 gene compared to 163 cases (78%) that had accumulation or aberrant expression of the protein, as detected by immunohistochemical staining. Point mutations accounted for 80.4% (87/107) of all genetic changes. The specimens from northern China exhibited fewer p53 gene aberrations and a more even distribution of mutations in exons 5-8 compared to those from southern China in which 60% of all mutations were found in exon 5. A major hot spot was found at codon 176 in exon 5, where 41 samples from Shantou, Guangzhou, and Hong Kong had a G-->T transversion. It is likely that among southern Chinese this codon is susceptible to mutagenesis by carcinogens. Codons 175, 203, 245, 250, 273, and 282 were also shown to be mutational hot spots, with three or more mutations observed at each site. The p53 mutational data obtained in this study showed that Chinese esophageal carcinomas are often associated with some unique genetic alterations, which may be attributed to specific dietary or environmental carcinogens that affect the Chinese but not Caucasians.

Adult↗

PubMed1984

Carcinogen-induced mutation spectrum in wild-type, uvrA and umuC strains of Escherichia coli. Strain specificity and mutation-prone sequences.

Forward mutations induced by the ultimate carcinogen N-acetoxy-N-2-acetylaminofluorene (N-Aco-AAF) in the tetracycline resistance gene carried on plasmid pBR322 are shown to be dependent upon the induction of the host SOS functions in wild-type and umuC Escherichia coli cells. The mutation frequency in the umuC strain is equal to about 40% of the mutation frequency observed in the umu+ background. In the excision-repair-deficient uvrA mutant strain the mutagenic response is the same as in SOS-induced wild-type cells whether or not the uvrA bacteria are SOS-induced. Equal mutation frequencies are obtained in both the wild-type and the uvrA strains for equal modification levels although the survival of AAF-modified plasmid DNA is greatly reduced in the uvrA strain as compared to the wild-type strain. Sequence analysis of the mutations reveals that more than 90% of the N-Aco-AAF-induced mutations are frameshift mutations. Two types of mutational hotspots are observed occurring either at repetitive sequences or at non-repetitive sequences. Both types of mutants appear at similar locations and frequencies in both the wild-type and the uvrA strains. On the other hand, only the non-repetitive sequence mutants are obtained in the umuC background. These non-repetitive sequence mutants preferentially occur within the sequence 5' G-G-C-G-C-C 3' (the NarI restriction enzyme recognition sequence). The analysis of the -AAF binding spectrum to the same DNA fragment shows that there is no direct correlation between the modification spectrum and the mutation spectrum. We suggest that certain sequences are "mutation-prone" in the sense that only these sequences can be efficiently mutated as the result of an active processing mediated by specific proteins. When a sequence is said to be mutation-prone it probably corresponds to a particular structure that is induced within this sequence as a result of the binding to the DNA of the mutagen. This sequence-specific conformational change is the substrate for the protein(s) that fixes the mutation. The mutagenic processing pathway(s) is part of the cellular response to DNA-damaging agents (the so-called SOS response). Two pathways for frameshift mutagenesis are suggested by the data: an umuC-dependent pathway, which is involved in the mutagenic processing of lesions within repetitive sequences; an umuC-independent pathway responsible for the fixation of mutations within specific non-repetitive sequences.

2-Acetylaminofluorene↗

PubMed2006

Mutational spectrum and genotype-phenotype correlations in mevalonate kinase deficiency.

Mevalonate kinase deficiency (MKD) is an autosomal recessive autoinflammatory disorder caused by mutations in the MVK gene resulting in deficient activity of mevalonate kinase (MK). Depending on the clinical severity, MKD may present as hyper-IgD and periodic fever syndrome (HIDS) or the more severe mevalonic aciduria (MA). We analyzed the MVK gene in 57 patients with MKD and found 39 different mutations including 15 novel mutations, expanding the total mutational spectrum of MKD to 63 mutations. To get more insight into the genotype-phenotype correlation in MKD, we studied the effect of selected missense mutations on MK protein stability and activity in various patient fibroblast cell lines. All MKD cell lines showed markedly decreased MK activities that correlated well with the clinical severity and, for most of the cell lines, with the amount of MK protein. When fibroblasts of MKD patients were cultured under conditions known to promote a more controlled protein folding, all cell lines of patients with the HIDS phenotype and few cell lines of patients with the MA phenotype showed an increase in the residual MK activity. This increase in enzyme activity correlates well with an increase in the MK protein levels in these cell lines, indicating that most of the mutations in MKD affect stability and/or folding of the MK protein rather than affecting the catalytic properties of the enzyme. The finding that the residual activity in MKD can be manipulated by environmental conditions may offer therapeutic options to alleviate or prevent the clinical symptoms associated with MKD.

Alleles↗

PubMed1996

Reactive oxygen species may participate in the mutagenicity and mutational spectrum of cadmium in Chinese hamster ovary-K1 cells.

The molecular nature of mutations induced by Cd was investigated in this study to elucidate the role of Cd in the initiation of carcinogenesis. Exposing Chinese hamster ovary (CHO)-K1 cells to cadmium acetate markedly decreased the colony-forming ability of cells and induced mutation frequency in the hypoxanthine (guanine) phosphoribosyltransferase (hprt) gene. The mutation frequency induced by Cd at LD30-LD20 doses was approximately 20 times that of untreated cells. D-Mannitol, a scavenger of reactive oxygen species (ROS), significantly protects cells against Cd cytotoxicity and mutagenicity. Furthermore, non-cytotoxic doses of 3-amino-1,2,4-triazole, a catalase inhibitor, potentiates Cd cytotoxicity and mutagenicity. The cellular Cd uptake ability was not altered by the combined treatment with either D-mannitol or 3-amino-1,2,4-triazole. The GSH level and the activities of GSH peroxidase, GSSG reductase, and catalase in cells treated with Cd (4 microM, 4 h) decreased to 78%, 47%, 40%, and 22% of the untreated cells, respectively. Those enzymatic activities recovered to normal levels 8 h after removing Cd. Polymerase chain reaction and DNA sequencing analysis of 54 independent Cd mutants revealed Cd-induced base substitutions, splice mutations, and large genomic deletions. All six types of base substitutions were observed; however, base transversions (22/27; 81%) occurred more frequently than transitions (5/27; 19%). The frequencies of mutations occurring at T.A or G.C base pairs were roughly equal. Results in this study strongly suggest that Cd mutagenicity in CHO-K1 cells is ROS-dependent. Moreover, the unique mutational spectrum induced by Cd implies that specific DNA adducts generated through the interaction of Cd-DNA and ROS may play a role in the mutational specificity.

Animals↗

PubMed1996

Species-specific differences in hepatic mutant frequency and mutational spectrum among lambda/lacI transgenic rats and mice following exposure to aflatoxin B1.

In vivo mutations were studied in lambda/lacI (Big Blue) transgenic C57BL/6 mice and F344 rats following exposure to either AFB1 (aflatoxin B1) or DMSO vehicle. Fourteen days after exposure, livers were removed for DNA extraction and subsequent mutational analysis of the lacI gene. Mice injected with a single i.p. dose of AFB1 at 2.5 mg/kg did not show a significant increase in liver mutant frequency relative to vehicle-treated controls. DNA sequence analysis of lacI mutations collected from the AFB1-treated mice showed a pattern of mutation similar to that of the previously observed spontaneous mouse liver mutational spectrum. In contrast, rats subjected to one-tenth the mouse AFB1 dosage responded with an approximate 20-fold induction in liver mutant frequency over background. Sequencing of lacI mutations also revealed spectral differences between vehicle- and AFB1-treated rats. A large increase in G:C-->T:A transversions was observed among lacI mutations isolated from the AFB1-treated rats. This work is among the first multi-species in vivo mutagenicity studies using transgenic rodents harboring the same shuttle vector. Such multi-species in vivo assays may prove to be valuable in the areas of mechanistic analysis and risk assessment.

Aflatoxin B1↗

PubMed2003

Analysis of the human APC mutation spectrum in a saccharomyces cerevisiae strain with a mismatch repair defect.

Somatic APC mutations in colorectal tumors with an RER phenotype reflect excessive frameshift mutations, especially in simple repetition tracts within the coding sequence. Because this type of mutation is characteristic of cells with a deficient DNA MMR system, the APC mutation signature of RER tumors may be attributable to a defect in the MMR system. However, there is little experimental evidence to prove that the spectrum of mutations and the APC gene distribution are directly influenced by MMR system defects. We therefore examined the mutation spectrum of the MCR of the APC gene after transfection into both MMR-proficient and MMR-deficient yeast strains and compared it with a previously reported human APC mutation database. Small insertions or deletions in mono- or dinucleotide repeats were more common in the MMR-deficient than in the MMR-proficient strain (91.2% vs. 38.1%, Fisher's exact test p < 0.0001). Furthermore, the 2 mutation hot spots, 4385-4394(AG)(5) and 4661-4666(A)(6), found in the yeast system corresponded with those in human tumors. Combining our data with those from human tumors, there appears to be hypermutable mutations in specific simple repetitive sequences within the MCR, which are more prevalent in MMR-deficient cells and RER tumors than in MMR-proficient cells and non-RER tumors. We therefore consider that the differences in the spectra of RER and non-RER tumors are attributable at least in part to the MMR system of the host cells.

Adenomatous Polyposis Coli Protein↗

PubMed1992

Mutation spectrum of spontaneous frameshift revertants in yeast using double-strand gap repair.

A mutation spectrum was constructed from a series of randomly isolated spontaneous His+ revertants of the frameshift mutant his4-38 in Saccharomyces cerevisiae. For each true revertant, a 438 bp region encompassing his4-38 on chromosome III was recovered into a shuttle vector by double-strand gap repair. Of the 45 independent His+ revertants sequenced, 44 were -1 base deletions and one revertant was a +2 base insertion. The -1 deletions exhibited a bimodal distribution. Of the bases encompassing the his4-38 region from +153-181, approximately 45% were not involved in a reversion event, although a -1 frameshift within this region will result in a viable His+ revertant. Approximately 49% of -1 events occurred within runs of 3 repeated bases. At these sites the strand-slippage model for frameshift mutation is supported. However, the -1 events occurring at sites of 2 repeated bases and the low frequency (2%) of +2 base insertions suggest that the transiently misaligned template model is a significant mechanism in reversion of his4-38. When the distribution of -1 events at repeated bases was discounted, a hotspot involving a -T at position +163 was resolved.

Base Sequence↗

PubMed1992

Singlet oxygen induced mutation spectrum in mammalian cells.

In order to characterize the molecular nature of singlet oxygen (1O2) induced mutations in mammalian cells, a SV40-based shuttle vector (pi SVPC13) was treated with singlet oxygen arising from the thermal decomposition of the water-soluble endoperoxide of 3,3'-(1,4-naphthylidene) dipropionate (NDPO2). After the passage of damaged plasmid through monkey COS7 cells, the vector was shuffled into E. coli cells, allowing the screening of supF mutants. The mutation spectrum analysis shows that single and multiple base substitutions arose in 82.5% of the mutants, the others being rearrangements. The distribution of mutations within the supF gene is not random and some hotspots are evident. Most of the point mutations (98.4%) involve G:C base pairs and G:C to T:A transversion was the most frequent mutation (50.8%), followed by G:C to C:G transversion (32.8%). These results indicate that mutagenesis in mammalian cells, mediated by 1O2-induced DNA damage, is targeted selectively at guanine residues.

Animals↗

PubMed2004

Spontaneous mutant frequency and mutation spectrum for gene A of phiX174 grown in E. coli.

The use of transgenic targets for measuring mutant frequencies in mammalian tissue requires an estimate of the mutant frequency that results from recovery of the transgene in bacterial recovery systems. In this study, we have determined the spontaneous mutant frequency, estimated the mutation rate, and ascertained the mutation spectrum for gene A of phiX174 grown in E. coli strain CQ2 from 156 small independent cultures. The mutant frequency of 12 of the 156 cultures was 17 +/- 1.0 x 10(-6) and the estimated mutation rate per gene replication was 7.4 +/- 2.3 x 10(-6). The mutant frequency and spectrum from E. coli were not significantly different from that of solvent-treated embryonic mouse cells in culture, 19 +/- 0.5 x 10(-6) (Valentine CR et al. [2002]: Environ Mol Mutagen 39:55-68), indicating that those spontaneous mutants were primarily derived from E. coli. The E. coli spectrum was heavily weighted toward two major target sites (hot spots), 4225A-->G (56%) and 4218G-->A or C (20%). Four new target sites and one new mutational event were recovered by the gene A forward assay. A mutant spectrum from an expanded phage stock was also determined to assess the effects of propagating the virus. This mutant frequency was higher (6 x 10(-4)), contained more double mutants (15% compared to 0.6%), and had a significantly different spectrum from the spectrum for independent cultures (fewer A:T-->G:C and G:C-->C:G changes and more G:C-->A:T; P < 0.002). The E. coli mutation spectrum will be useful for determining the origin of gene A mutation in tissues of phiX174 transgenic mice.

Bacteriophage phi X 174↗

PubMed1995

Mutation spectrum of 2-chloroethyl methanesulfonate in Drosophila melanogaster premeiotic germ cells.

The 2-chloroethyl methanesulfonate (2ClEMS)-induced alcohol dehydrogenase (Adh) null germline mutation frequency in treated Drosophila melanogaster second instar larval gonia was two orders of magnitude greater than the spontaneous mutation frequency. DNA sequence analysis of 83 Adh null mutations showed that 40 mutations of independent origin were at 23 sites in the Adh gene. The mutation spectrum contained only GC-->AT transitions with 35 mutations (87.5%) at the middle or 3' guanine. In addition, characteristics of glutathione (GSH)-mediated bioactivation were determined for 2ClEMS in vitro. Rates of GSH-mediated conjugation, catalyzed by purified rat liver glutathione-S-transferase (GST), and binding of [35S]GSH-mediated conjugation products to calf thymus DNA were determined for 2ClEMS, 1,2-dichloroethane (EDC) and 1,2-dibromoethane (EDB). The relative rates of GSH-mediated conjugation were the following: 5 mM EDB > 40 mM 2ClEMS > 40 mM EDC. A similar trend was observed for DNA binding of the [35S]GSH-mediated conjugation products when differences in mutagen concentration were considered: EDB > 2ClEMS > EDC. The ratios of DNA binding to GSH conjugation calculated for EDB, EDC and 2ClEMS were 6.8 x 10(-5), 9.3 x 10(-5) and 19.1 x 10(-5), respectively. A narrow range, less than a 3-fold difference, in the ratios of DNA binding to GSH conjugation indicates that the bioactivation of 2ClEMS is mediated by the same mechanism as EDB and EDC. Consequently, 2ClEMS, EDC and EDB may induce a specific mutation in premeiotic germ cells.

Alcohol Dehydrogenase↗

PubMed2004

LET and ion-species dependence for mutation induction and mutation spectrum on hprt locus in normal human fibroblasts.

We have been studying LET and ion species dependence of RBE in mutation frequency and mutation spectrum of deletion pattern of exons in hprt locus. Normal human skin fibroblasts were irradiated with heavy-ion beams, such as carbon- (290 MeV/u and 135 MeV/u), neon- (230 MeV/u and 400 MeV/u), silicon- (490 MeV/u) and iron- (500 MeV/u) ion beams, generated by Heavy Ion Medical Accelerator in Chiba (HIMAC) at national Institute of Radiological Sciences (NIRS). Mutation induction in hprt locus was detected to measure 6-thioguanine resistant colonies and deletion spectrum of exons was analyzed by multiplex PCR. The LET-RBE curves of mutation induction for carbon- and neon-ion beams showed a peak around 75 keV/micrometers and 155 keV/micrometers, respectively. On the other hand, there observed no clear peak for silicon-ion beams. The deletion spectrum of exons was different in induced mutants among different ion species. These results suggested that quantitative and qualitative difference in mutation occurred when using different ion species even if similar LET values.

Carbon↗

PubMed2003

UVA-induced cyclobutane pyrimidine dimers form predominantly at thymine-thymine dipyrimidines and correlate with the mutation spectrum in rodent cells.

Ligation-mediated PCR was employed to quantify cyclobutane pyrimidine dimer (CPD) formation at nucleotide resolution along exon 2 of the adenine phosphoribosyltransferase (aprt) locus in Chinese hamster ovary (CHO) cells following irradiation with either UVA (340-400 nm), UVB (295-320 nm), UVC (254 nm) or simulated sunlight (SSL; lambda > 295 nm). The resulting DNA damage spectrum for each wavelength region was then aligned with the corresponding mutational spectrum generated previously in the same genetic target. The DNA sequence specificities of CPD formation induced by UVC, UVB or SSL were very similar, i.e., in each case the overall relative proportion of this photoproduct forming at TT, TC, CT and CC sites was approximately 28, approximately 26, approximately 16 and approximately 30%, respectively. Furthermore, a clear correspondence was noted between the precise locations of CPD damage hotspots, and of 'UV signature' mutational hotspots consisting primarily of C-->T and CC-->TT transitions within pyrimidine runs. However, following UVA exposure, in strong contrast to the above situation for UVC, UVB or SSL, CPDs were generated much more frequently at TT sites than at TC, CT or CC sites (57% versus 18, 11 and 14%, respectively). This CPD deposition pattern correlates well with the strikingly high proportion of mutations recovered opposite TT dipyrimidines in UVA- irradiated CHO cells. Our results directly implicate the CPD as a major promutagenic DNA photoproduct induced specifically by UVA in rodent cells.

Adenine Phosphoribosyltransferase↗

PubMed1992

Mutational spectrum at the Hprt locus in splenic T cells of B6C3F1 mice exposed to N-ethyl-N-nitrosourea.

We have determined the mutational spectrum of N-ethyl-N-nitrosourea (ENU) in exon 3 of the hypoxanthine (guanine) phosphoribosyltransferase gene (Hprt) in splenic T cells following in vivo exposure of male B6C3F1 mice (5-7 weeks old) to ENU. Hprt- mutants were isolated by culturing splenic T cells in microtiter dishes containing medium supplemented with interleukin 2, concanavalin A, and 6-thioguanine. DNA was extracted from 6-thioguanine-resistant colonies and amplified by the polymerase chain reaction (PCR) using primers flanking Hprt exon 3. Identification of mutant sequences and purification of mutant DNA from contaminating wild-type Hprt DNA was accomplished by denaturing-gradient gel electrophoresis. Purified mutant DNA was then sequenced. Treatment of mice with ENU at 40 mg/kg of body weight produced a Hprt- mutant frequency of 7.3 x 10(-5) in splenic T cells, approximately 35-fold above background levels. Sixty-nine of the 521 Hprt- mutants analyzed contained mutations in exon 3 (13%). Transversions and transitions at A.T base pairs dominated the spectrum; 62 of the 69 exon 3 mutations were at A.T base pairs (14 different sites). Thirteen of 14 thymine bases undergoing mutation (61 of 62 mutations at A.T bases) were located on the nontranscribed strand of exon 3. The majority of the remaining mutations (6 of 69) were transitions at a single G.C base pair. These results suggest the importance of thymidine alkylation in ENU-induced mutagenesis in vivo. The mouse Hprt- T-cell cloning/sequencing assay described here may represent a useful system for studying the molecular mechanism of chemically induced mutation occurring in vivo in an endogenous gene.

Animals↗

PubMed2006

Mutational spectrum of the lacI gene in Escherichia coli K12 induced by low-energy ion beam.

The mutational spectrum of the genomic lacI gene induced by low-energy nitrogen ion irradiation in wild type Escherichia coli strain W3110 were compared with the spontaneous and the vacuum controls. The mutant frequency of irradiated group was dose-dependent and reached 26.3 x 10(-6) at dose of 31.2 x 10(14) ions/cm2, which was about 18-fold over the background (1.5 x 10(-6)) and 10-fold over the vacuum controls (2.6 x 10(-6)). This result indicated that the low-energy ion irradiation was one of many effective mutagens, though the vacuum condition of low-energy ions contributed some low-level gene mutations. It was found that the difference between the spontaneous and the vacuum control was the increases of base-pair substitutions in the vacuum control group. The spectra of irradiated group were quite similar to that of oxygen free-radical induced in the same strain, suggesting free-radicals and other adducts generated by low-energy ions might play an important role in the mutagenesis in vivo. When the spontaneous and the vacuum control group were compared, base-pair substitutions, deletions and additions of the irradiated group were significantly increased, and the +TGGC or -TGGC at hot spot was decreased from 82 to 48%. But the remarkable increase in absolute MF of the +TGGC or -TGGC at hot spot in the irradiated group suggested that low-energy ions did induce the mutations of this type. The spectra of our irradiated group had relative low-level base-pair substitutions, high-level +/-TGGC and high proportion additions than those of gamma-radiation induced, implying there were some different effects or processes between them.

Bacterial Proteins↗

PubMed2006

BRCA1 and BRCA2 germline mutational spectrum and evidence for genetic anticipation in Portuguese breast/ovarian cancer families.

We present the first characterisation of the mutational spectrum of the entire coding sequences and exon-intron boundaries of the BRCA1 and BRCA2 genes as well as large BRCA1 rearrangements in Portuguese families with inherited predisposition to breast/ovarian cancer. Of the 100 probands studied, pathogenic mutations were identified in 22 (24.7%) of 89 breast and/or ovarian cancer families with more than one affected member (15 in BRCA1 and seven in BRCA2), but in none of the 11 patients without family history of cancer. One (6.7%) of the BRCA1 mutations is a large deletion involving exons 11-15. Seven pathogenic point mutations are novel: 2088C>T, 2156delinsCC, and 4255_4256delCT in BRCA1 and 4608_4609delTT, 5036delA, 5583_5584insT, and 8923C>T in BRCA2. The novel 2156delinsCC was identified in three probands from different families and probably represents a founder mutation in our population. We also found a previously reported 3450_3453del4 mutation in three unrelated patients. In addition to the 22 pathogenic mutations, we identified 19 missense mutations of uncertain pathogenic significance, three of them (5241G>C in BRCA1 and IVS6+13C>T and 3731T>C in BRCA2) previously undescribed. The percentage of cases with truncating mutations in BRCA1 and BRCA2 was higher in breast/ovarian cancer (37.0%, mostly BRCA1) and male breast cancer (40%, all BRCA2) families than in families with only female breast cancer (17.5%). Interestingly, we found evidence for genetic anticipation regarding age at diagnosis of both breast and ovarian cancer in those families presenting affected members in more than one generation. These findings should be taken into consideration while planning screening and prophylactic measures in families with inherited predisposition to breast and ovarian cancer.

Adolescent↗

PubMed2006

Mutation spectrum induced by dihydropyrazines in Escherichia coli.

Dihydropyrazine (DHP), which induces mutagenesis in E. coli, was investigated. From analyzing mutations in the chromosomal rpoB gene, the mutation spectrum in uvrB strain revealed the different behavior on exposure to two DHP derivatives 3-hydro-2,2,5,6-tetramethylpyrazine (HTMP), and 2,3-dihydro-5,6-dimethylpyrazine (DHDMP). A higher level of DHP-induced mutation was observed, with base substitutions at G : C pairs predominant. HTMP and DHDMP increased the frequency of G : C to T : A transversions. HTMP increased the frequency of G : C to A : T transitions, than did DHDMP. These findings suggest that DHPs prefer to attack the G : C pair and that different DHP derivatives may prefer distinct mutagenic base pairs; and further, that nucleotide excision repair may be involved in the repair of DHP-induced mutations.

Antibiotics, Antitubercular↗