RESUMO
A minitransposon mutant of Salmonella enterica serovar Typhimurium SR-11, SR-11 Fad(-), is unable to utilize gluconeogenic substrates as carbon sources and is avirulent and immunogenic when administered perorally to BALB/c mice (M. J. Utley et al., FEMS Microbiol. Lett., 163:129-134, 1998). Here, evidence is presented that the mutation in SR-11 Fad(-) that renders the strain avirulent is in the cra gene, which encodes the Cra protein, a regulator of central carbon metabolism.
Assuntos
Proteínas de Bactérias/genética , Genes Bacterianos , Proteínas Repressoras/genética , Salmonella typhimurium/metabolismo , Salmonella typhimurium/patogenicidade , Animais , Metabolismo dos Carboidratos , Ciclo do Ácido Cítrico , Intestinos/microbiologia , Macrófagos Peritoneais/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Muco/microbiologia , Mutagênese Insercional , Salmonella typhimurium/genética , SorotipagemRESUMO
Numerous studies have associated colorectal adenoma with smoking and large bowel cancer with consumption of foods potentially containing polycyclic aromatic hydrocarbons. Enhanced metabolic activation of polycyclic aromatic hydrocarbons has recently been observed in homozygotes for a MspI mutation in the 3'-end of CYP1A1. We conducted a population-based case-control study to investigate whether CYP1A1 polymorphisms were related to colorectal cancer risk. Using polymerase chain reaction-based methods, we assessed the frequency of the MspI polymorphism in the 3'-end of CYP1A1 and another mutation in exon 7 of the gene (Ile-Val polymorphism) among 43 patients with in situ adenocarcinoma of the large bowel and 129 population controls. Homozygosity for the MspI mutant genotype was found to be positively associated with in situ colorectal cancer in Japanese (P = 0.008) and Hawaiians/part-Hawaiians (P < 0.001), whereas the study lacked power to detect a similar association in Caucasians. The odds ratio for the homozygous variant genotype compared to the heterozygous and wild-type genotypes was 7.9 (95% confidence interval, 1.4-44.4) in Japanese. A similar association was suggested for the exon 7 mutation homozygosity in Japanese, as the two polymorphisms are in genetic disequilibrium. Thus, this study suggests a potentially important role for CYP1A1 and polycyclic aromatic hydrocarbons in the etiology of colorectal cancer in populations with a high gene frequency.
Assuntos
Neoplasias Colorretais/genética , Sistema Enzimático do Citocromo P-450/genética , Adulto , Idoso , Sequência de Bases , Estudos de Casos e Controles , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Compostos Policíclicos/metabolismo , Polimorfismo de Fragmento de RestriçãoRESUMO
The human cytomegalovirus open reading frames (ORFs) UL119 through UL115 (UL119-115) are located downstream of the immediate-early 1 and 2 transcription units. The promoter upstream of UL119 is active at all times after infection and drives the synthesis of a spliced 3.1-kb mRNA. The viral mRNA initiates in UL119, contains UL119-117 and UL116, and terminates just downstream of UL115. True late transcripts that are detected only after viral DNA synthesis originate from this transcription unit. True late mRNAs of 2.1 kb, containing ORFs UL116 and UL115, and 1.2 kb, containing ORF UL115 only, are synthesized. The true late viral mRNAs are 3' coterminal with the 3.1-kb mRNA. This transcription unit is an example of late promoters nested within an immediate-early-early transcription unit. The gene products of UL119-117, UL116, and UL115 are predicted to be glycoproteins. Efficient expression of the downstream ORFs at late times after infection may be related to alternate promoter usage and downstream cap site selection.
