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R Devoret

Publications and source records attributed to R Devoret.

At least 55 records · Page 3Linked to original sources
PubMed1980

Induction of prophage lambda by daunorubicin and derivatives correlation with antineoplastic activity.

The antineoplastic drug daunorubicin and 15 other anthracyclines were tested for their ability to induce prophage lambda in Escherichia coli K12. Prophage lambda induction by daunorubicin was obtained in excision-repair deficient uvr- bacteria at doses about 3-fold lower than in excision-repair proficient uvr+ cells; this suggests that some of the lesions produced in DNA by daunorubicin are subject to excision repair and may be adducts. Daunorubicin seems to be converted to active species capable of causing prophage inducing lesions in DNA by bacterial enzymes. The antineoplastic and prophage inducing potencies of the anthracyclines were compared in a blind test. These two parameters were correlated for two thirds of the compounds. Such a correlation supports the idea that the antineoplastic activity of the anthracyclines is a consequence of their capacity to damage DNA.

Antibiotics, Antineoplastic↗
PubMed1980

Induction of prophage lambda does not require full induction of RecA protein synthesis.

In mitomycin C-treated lambda lysogens, even though the rate of synthesis of RecA protein was greatly reduced by a low concentration of rifampicin (4 microgram/ml), induction of prophage lambda occurred readily as assessed by (i) cell lysis of the lysogens, (ii) production of progeny phage, and (iii) extensive cleavage of lambda repressor. The extent and the rate of cleavage of lambda repressor were not significantly affected by the low rate of synthesis of RecA protein resulting from rifampicin action. However, the yield of phage progeny was reduced and lysis of the cells was slightly delayed. We conclude that in RecA+ bacteria, induction of prophage lambda does not require full induction of RecA protein synthesis.

Autoradiography↗
PubMed1979

Repair promoted by plasmid pKM101 is different from SOS repair.

In E. coli K12 bacteria carrying plasmid pKM101, prophage lambda was induced at UV doses higher than in plasmid-less parental bacteria. UV-induced reactivation per se was less effective. Bacteria with pKM101 showed no alteration in their division cycle. Plasmid pKM101 coded for a constitutive error-prone repair different from the inducible error-prone repair called SOS repair. Plasmid pKM101 protected E. coli bacteria from UV damage but slightly sensitized them to X-ray lesions. Protection against UV damage was effective in mutant bacteria deficient in DNA excision-repair provided that the recA, lexA and uvrE genes were functional. Survival of phages lambda and S13 after UV irradiation was enhanced in bacteria carrying plasmid pKM101; phage lambda mutagenesis was also increased. Plasmid pKM101 repaired potentially lethal DNA lesions, although wild-type DNA sequences may not necessarily be restored; hence the mutations observed are the traces of the original DNA lesions.

DNA Repair↗
PubMed1978

Expression of a bacterial gene turned on by a potent carcinogen.

Contrary to mutagenesis, lysogenic induction produced by chemical carcinogens occurs in the majority of a population of lysogenic cells. Such a mass effect can therefore be measured at the biochemical level using an E. coli tester strain in which the galactose operon has been put under the negative control of the lambda repressor. In this publication we show that galactokinase synthesis is turned on by aflatoxin B1 metabolites within an hour after treatment of the tester bacteria. Such a biochemical assay provides a useful means for identifying potential chemical carcinogens.

Aflatoxins↗
PubMed1977

Induced reactivity of UV-damaged phage gamma in E. coli K12 host cells treated with aflatoxin B1 metabolites.

The metabolites of aflatoxin B1, the most potent hepatocarcinogen so far known, promote in E. coli K12 cells the reactivation of phage lambda damaged by ultraviolet (UV) radiation. This reactivation process is error prone; 25% of the phage DNA lesions are repaired, but mutagenesis, scored as clear plaque formation, is increased as much as 10-fold. Such reactivation of UV-damaged phage lambda, which occurs in wild-type and in uvrA but not in recA bacteria, is inducible: phage reactivation is obtained even after a long delay following treatment of the host by the short-lived metabolites. This induced reactivation of UV-damaged phage in hosts treated with metabolites of aflatoxin B1 is similar to direct of indirect UV reactivation. Metabolites of aflatoxin B1 produce induced phage reactivation as well as prophage lambda induction in lysogens and cell filamentation in non-lysogens. These cellular events are also triggered by DNA lesions caused by UV radiation and result from the induction of a metabolic pathway (SOS functions). We postulate that, in eucaryotes, carcinogens may induce cellular SOS functions similar to those in E. coli. Induction of such functions might be responsible for the transformation of mammalian cells.

Aflatoxins↗
PubMed1977

Characterization of lexB mutations in Escherichia coli K-12.

Two mutations have been located at the recA locus and phenotypically characterized along with a third one, previously called rec-34. The three mutants behaved similarly to lexA mutants. They were sensitive to ultraviolet (UV) light and X rays, and lambdaFec- phages were able to plate on them. The three mutations were called lexB because they could be distinguished from recA mutations by the last property. lexB mutants were less sensitive to UV and X irradiations than were recA mutants and were, to various degrees, recombination proficient. UV light failed to induce prophage lambda in all three lexB lysogens. In contrast, thymine starvation induced lexB31 and lexB34 lysogens. In lexB34 mutants, but not in lexB30 and lexB31 mutants, UV reactivation occurred at a low level. In Escherichia coli K-12, the recA gene has basic functions in the repair of deoxyribonucleic acid lesions, deoxyribonucleic acid recombination, and prophage induction. The three lexB mutations alter unequally and independently the three functions. This suggests that the recA and lexB mutations affect the same gene.

Chromosome Mapping↗
PubMed1976

Prophage lambda induction of Escherichia coli K12 envA uvrB: a highly sensitive test for potential carcinogens.

A simple, inexpensive, and sensitive test for potential carcinogens based upon the property of carcinogens to induce prophage lambda is described. By using chemicals activated with microsomal enzymes and E. coli K12 permeable (envA) tester bacteria also deficient in DNA repair (uvrB), the range of carcinogens detected in a lysogenic induction test (inductest) has been extended. We have provided the evidence that, after activation, carcinogenic polycyclic hydrocarbons such as benzo[a5pyrene and 7,12-dimethylbenz[a]anthracene induce prophage lambda. Three variants of the test have been developed (inductests I, II, and III), which are as sensitive as the mutagenicity test of Ames et al. [Ames, B. N., McCann, J. and Yamasaki, E. (1975) Mutat. Res. 31, 347-364]. Inductests II and III provide a quantitative estimation of the inducing activity of a carcinogen. With the latter test, one can determine: (i) the cellular toxic effect of a carcinogen and (ii) the kinetics of appearance and disappearance of active metabolites. For two series of chemicals, aflatoxins and benz[a]anthracenes, there is a good correlation between their carcinogenic activity in rodents and their prophage inducing activity in bacteria. The fact that the majority of the cell population is induced makes it possible to test the inducing activity of carcinogens at the biochemical level, e.g., by measuring lambda repressor inactivation.

Biotransformation↗
PubMed1975

Recovery of phage lambda from ultraviolet damage.

Recovery of phage lambda from ultraviolet damage can occur, in the dark, through three types of repair processes as defined by microbiological tests: (1) host-cell reactivation, (2) prophage reactivation, and (3) UV reactivation. This paper reviews the properties of the three repair processes, analyzes their dependence on the functioning of bacterial and phase genes, and discusses their relationship. Progress in the understanding of the molecular mechanisms underlying the three repair processes has been relatively slow, particularly for UV reactivation. It has been shown that host-cell reactivation is due to pyrimidine dimer excision and that prophage reactivation is due to genetic recombination (prereplicative). We provide evidence showing that neither of these mechanisms accounts for UV reactivation of phage lambda. Furthermore, UV reactivation differs from the other repair processes in that it is inducible and error-prone. Whether UV-damaged bacterial DNA is subject to a similar repair process is still an open question.

Cell Survival↗
PubMed1975

Induction and mutagenesis of prophage lambda in Escherichia coli K12 by metabolites of aflatoxin B1.

Like most carcinogens, aflatoxin B1 must be activated by mammalian microsomal enzymes to give rise to coupounds active on bacteria. These compounds act as inducers of E. coli K12 (lambda) at a high efficiency, whereas unmodified aflatoxin B1 has no effect. Moreover, metabolites of aflatoxin B1 have a mutagenic action on phage lambda, as shown by the appearance of clear plaque mutants. We propose the hypothesis that the same derivative is responsible for carcinogenesis of liver cells by aflatoxin B1. Therefore, our system provides a simple way of measuring in vitro, in the same assay, the mutagenic and inducing activities of compounds to which the cells are permeable, thereby detecting potentially carcinogenic agents.

Aflatoxins↗