EFFECT OF CHEMICAL MODIFIERS ON INACTIVATION AND MUTATION-INDUCTION BY GAMMA RADIATION IN ESCHERICHIA COLI
In continuation of earlier studies demonstrating sensitization by N- ethylmaleimiede (NEM) and of protection by dimethyl sulfoxide and thiourea when inactivation of colony forming ability was the criterion of radiation damage, the influence of these compounds, together with the familiar modifiers oxygen, glycerol and cysteine, was investigated using an additional criterion of radiation effect, namely mutation. Reversions to tryptophan independence in strain WP 2 of E. coli B/r were studied. Cobalt-60 gamma radiation was given at room temperature in a glass vessel at the rate of 4500 rad/min; air or oxygen- free nitrogen was bubbled through the bacterial suspension for 6 min before and throughout irradiation. Neither NEM nor oxygen had any effect on the spontaneous mutation rate, but they enhanced both radiation-induced mutation and inactivation. For inactivation the enhancement ratios, based on slopes of survival curves, were greater for oxygen and for NEM + oxygen which were identical) than for NEM alone. When the enhancement ratios were based on the doses needed to produce a given effect (e.g. G = 300), it appeared that the mutation enhancement ratio for oxygen + NEM was significantly less than that for oxygen alone, and that treatment with NEM + oxygen was not strictly dose-modifying. It is suggested that a constant small proportion of mutants is not expressed when NEM is present under aerobic conditions. When all the protective agents were tested under conditions of strict anoxia, thus eliminating oxygendepletion as a cause of apparent protection, none of the chemicals tested affected the spontaneous mutation rate. With the possible exception of cysteine, the treatments were not dose-modifying; protection was shown only at doses greater than 10-15 krad. With glycerol, for example, this threshold effect was shown whether the compound was added 6 or 26 min before irradiation, indicating that the threshold is not due to a requirement for preincubation with the compound. Glycerol, cysteine, and thiourea protected against mutation-induction and inactivation to the same extent, whereas dimethyl sulfoxide was appreciably less efficient at protecting against mutation-induction than against inactivation. It was shown previously that NEM enhances the lethal action of radiation only when present during irradiation; in this respect it resembles oxygen. It is suggested that NEM and oxygen are both able to combine with reactive sites which appear during irradiation on important biological molecules. The sites which react with oxygen are not known but it is suggested that those which react with NEM might be -SH groups or -S free radicals. Thus, proteins must be intimately involved in sensitization, and hence in mutation, since they are the only large sulfur- containing molecules of importance to the cell. The present results are difficult to reconcile with this hypothesis of mutations arising as a result of changes in DNA. In contrast to the specificity of sensitization, chemical protection seems to be a fairly uniform and general phenomenon and largely independent of the nature of the targets, as seen by these results with thiourea, glycerol, and cysteine. With dimethyl sulfoxide, however, significantly less protection was afforded against mutationinduction than against inactivation; it may have difficulty in penetrating sufficiently near to the locus which determines tryptophan-dependence. (BBB)
- Research Organization:
- Medical Research Council, Harwell, Berks, Eng.
- Sponsoring Organization:
- USDOE
- NSA Number:
- NSA-18-000126
- OSTI ID:
- 4164570
- Journal Information:
- Journal of General Microbiology (England), Vol. Vol: 31; Other Information: Orig. Receipt Date: 31-DEC-64
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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Related Subjects
ABSORPTION
ALCOHOLS
AMINO ACIDS
ANIONS
BACTERIA
CERIUM COMPOUNDS
COBALT 60
CYSTEINE
DECONTAMINATION
DISTRIBUTION
DNA
ESCHERICHIA COLI
ETHYL RADICALS
EXTRACTION COLUMNS
FREE RADICALS
GAMMA RADIATION
GLASS
GLYCERIN
HYDROCHLORIC ACID
IMIDES
ION EXCHANGE MATERIALS
LEAD OXIDES
MALEIC ACID
METABOLISM
METHYL RADICALS
MOLECULES
MUTATIONS
NITRIC ACID
NITROGEN
NITROGEN COMPOUNDS
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXYGEN
PROTEINS
QUANTITATIVE ANALYSIS
QUANTITY RATIO
RADIATION DOSES
RADIATION EFFECTS
RADIATION INJURIES
RADIATION PROTECTION
RECOVERY
RESINS
SEPARATION PROCESSES