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Biomedical subjects

J Cairns

Publications and source records attributed to J Cairns.

At least 145 records · Page 8Linked to original sources
PubMed1980

Efficiency of the adaptive response of Escherichia coli to alkylating agents.

When cultures of Escherichia coli are exposed to a low level of the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) they accumulate mutations for about 20 min and then become resistant to further mutagenesis by that level of MNNG. This 'adaptive response, has been shown to be due, at least in part, to induction of the rapid repair of O6-alkylguanine which appears to be the main mutagenic and carcinogenic lesion produced by simple alkylating agents. A similar kind of repair has been demonstrated in the livers of rats exposed to nitrosamines, and this presumably helps to protect animals against carcinogenesis by the various alkylating agents thjat are widespread in our environment. It seemed important, therefore, to find out just how effectively such adaptive responses can control mutations rates.

Adaptation, Physiological↗
PubMed1980

The Leeuwenhoek Lecture, 1978. Bacteria as proper subjects for cancer research.

Cancers are clones of abnormal cells, arising presumably as the result of mutational or epignetic alterations of gene expression. The kinetics of appearance of spontaneous cancers in populations of multiplying cells (i.e. the relation between age and cancer incidence) will therefore depend, among other things, on how these populations are organized and, in general, on the kinetics of the response of cells to prolonged mutagenesis. The organization of cell renewal in epithelia (i.e. the arrangement of cell lineages) is still rather obscure; in particular, it is not known to what extent the properties and organization of the stem cells tend to protect them from accumulating mutations. We have tried to mimic the arrangement of epithelia by attaching multiplying bacteria to filters. Study of mutagenesis in long-term cultures of such anchored bacterial has led to the discovery of some additional pathways for DNA repair which also appear to operate in mammalian cells.

Adaptation, Biological↗
PubMed1980

Sleep and depression: a case study of EEG sleep prior to relapse.

By chance, we were able to record for five consecutive nights the sleep of a 61-year-old woman before each of two successive depressive episodes. In this patient, marked changes in EEG sleep (notably a decline in "sleep efficiency") preceded both episodes. These changes are considered to be of predictive, but not of etiological, significance.

Bipolar Disorder↗
PubMed1979

Five variations of sleep deprivation in a depressed woman.

Systematic variation in aspects of the sleep-wakefulness cycle of a depressed woman showed that recovery occurred reliably after 19 to 20 hours sustained wakefulness, unrelated to diurnal rhythm. Depression returned during as little as 15 minutes sleep. The effect of sleep deprivation was a specific response, probably unrelated to REM sleep.

Aged↗
PubMed1978

The effects of a simulated refinery effluent on the grass shrimp, Palaemonetes pugio.

Duplicate static bioassays were conducted using a simulated refinery effluent on the grass shrimp (Palaemonetes pugio, Hippolyte sp.) with the LC-50 values recorded at 4-, 8-, 24-, 48-, and 96-hr intervals. The stimulated refinery effluent contained phenol (0.10 mg/L), sulfide (0.17 mg/L), chromium (0.25 mg/L), ammonia (10 mg/L), No. 2 fuel oil (10 mg/L), and kaolinite (20 mg/L). This arbitrary reference mixture (ARM) contains approximately the concentration of compounds recommended by EPA for 1977. Of the six ARM components, No. 2 fuel oil was the most toxic followed in decreasing order by sulfide, ammonia, phenol, chromium, and kaolinite. Temperature was the most important environmental variable affecting short term toxicity of the ARM to the grass shrimp. Light intensity, photo-period, and salinity had no significant effect. There was no difference in sensitivity of grass shrimp collected from five locations along the gulf and eastern coasts of the United States. Similarly, there was no difference in the response of two grass shrimp genera, Palaemonetes and Hippolyte to the ARM and there was no differences among the three species of Palaemonetes tested. In comparing the sensitivities of the two genera of grass shrimp and the pinfish (Lagodon rhombroides) to the ARM, the grass shrimp were more sensitive.

Animals↗
PubMed1978

Pathways of mutagenesis and repair in Escherichia coli exposed to low levels of simple alkylating agents.

Mutagenesis by simple alkylating agents is thought to occur by either a lexA+-dependent process called error-prone repair or a lex-independent process often attributed to mispairing during replication. We show here that error-prone repair is responsible for the majority of mutants formed after a large dose of alkylating agent, but it is unlikely that it contributes significantly to mutagenesis during exposure to low concentrations of these chemicals. The mutagenicity of these low doses of alkylating agent is reduced by a repair system constitutively present in lexA+ cells but absent in lexA mutants. This system reduces mutagenesis until a second error-free system, called the adaptive responses, can be induced [P. Jeggo, M. Defais, L. Samson, and P. Schendel, Mol. Gen. Genet, 157:1-9, 1977; L. Samson and J. Cairns, Nature (London) 267:281-283, 1977]. The adaptive response is capable of dealing with a much larger amount of alkylation damage than the constitutive system and, when induced, appears to be able to reduce mutagenesis by both decreasing the number of sites available for mutagenesis and delaying the induction of error-prone repair enzymes. Finally, we discuss a model of chemically induced mutagenesis based on these findings which maintains that the observed mutation frequency is dependent on a "race" between these two error-free systems and the two mutagenic pathways.

Alkylating Agents↗