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When human lymphocytes are treated with [3H]thymidine ([ 3H]dThd), the observed number of chromosomal aberrations induced by [3H]dThd and subsequent doses of X-rays is less than the number induced by X-rays alone. Experiments in which cells were examined at various times after exposure to the X-rays showed that this phenomenon, termed an adaptive response to the endogenous radiation from tritium, is not an artefact caused by radiation-induced mitotic delays, which could result in the sampling of metaphase cells that were irradiated in different parts of the G2 phase of the cell cycle, where sensitivity to X-rays changes dramatically. Reconstruction experiments in which labelled female cells were co-cultured with unlabelled male cells now show that labelled and unlabelled cells progress to metaphase equally, and therefore that the adaptive response is not the result of selection against a radiosensitive population of cells that have incorporated [3H]dThd. Measurements of chromosomal aberrations induced in the labelled female cells and unlabelled male cells that had been co-cultured show that the adaptive response is restricted to those cells exposed to radiation from the incorporation of [3H]dThd and that diffusible factors are not involved. The results are consistent with the proposal that this adaptive response is the result of the induction of a hitherto unknown chromosomal repair mechanism. It has now been found that this repair mechanism is induced at levels of radiation from [3H]dThd that in themselves are too low to induce any discernible chromosomal aberrations and that its activity is dependent on the enzyme poly(ADP-ribose) polymerase, because 3-aminobenzamide, an inhibitor of poly(ADP-ribosyl)ation, prevents the adaptive response.

Effects of phenobarbital (PB), carbamazepine (CBZ) and sodium valproate (VPA) monotherapy on endocrine functions were investigated in 7 clinically prepubertal children aged 5-10 8/12 years. The following meaning results were observed: normal PRL release, low basal T4 levels in PB-, CBZ-treated children and normal T4 basal level in the VPA-treated child; normal T3, rT3, TBG and TSH basal values and normal TSH release in all treated children, normal FSH release in PB-, CBZ- and VPA-treated females, high LH levels before and after LHRH injection in CBZ- and PB-treated females; normal levels in the VPA-treated one, normal basal FSH levels and increased releases in PB- and CBZ-treated males, high LH levels before and after LHRH injection in PB- and CBZ-treated males, normal basal and peak levels of GH.

Human lymphocytes exposed to low doses of ionizing radiation from incorporated tritiated thymidine or from X-rays become less susceptible to the induction of chromatid breaks by high doses of X-rays. This response can be induced by 0.01 Gy (1 rad) of X-rays, and has been attributed to the induction of a repair mechanism that causes the restitution of X-ray-induced chromosome breaks. Because the major lesions responsible for the induction of chromosome breakage are double-strand breaks in DNA, attempts have been made to see if the repair mechanism can affect various types of clastogenic lesions induced in DNA by chemical mutagens and carcinogens. When cells exposed to 0.01 Gy of X-rays or to low doses of tritiated thymidine were subsequently challenged with high doses of tritiated thymidine or bleomycin, which can induce double-strand breaks in DNA, or mitomycin C, which can induce cross-links in DNA, approximately half as many chromatid breaks were induced as expected. When, on the other hand, the cells were challenged with the alkylating agent methyl methanesulfonate (MMS), which can produce single-strand breaks in DNA, approximately twice as much damage was found as was induced by MMS alone. The results indicate that prior exposure to 0.01 Gy of X-rays reduces the number of chromosome breaks induced by double-strand breaks, and perhaps even by cross-links, in DNA, but has the opposite effect on breaks induced by the alkylating agent MMS. The results also show that the induced repair mechanism is different from that observed in the adaptive response that follows exposure to low doses of alkylating agents.

Cultures of blood from healthy adults were irradiated 48 h after stimulation with 240 R of X-rays and fixed after various time intervals (0-2 h, 2-4 h, 4-6 h). 3HTdR was added to several cultures after irradiation. Mitotic and labelling indices were used to distinguish between two cell samples inside the irradiated G2 population: D- cells reaching mitosis without mitotic delay and a high frequency of chromatic breaks and D+ cells with mitotic delay and which, during the delay, repair most of the damage produced. After R banding 450 chromatid deletions were located in each of the two cell samples. The D+ cells showed a higher frequency of breaks than the D- cells with decreasing chromosome size, in the telomeric and centromeric region and in the junction between the R+ and R- bands. These results can be interpreted as indicative of a non-random distribution of repair processes both between and within chromosomes.

When human lymphocytes were cultured with [3H]thymidine, which acts as a source of low-level chronic radiation, and then exposed to 150 rad of x-rays at 5, 7, 9, or 11 hours before fixation, the yield of chromatid aberrations was less than the sum of the yields of aberrations induced by [3H]thymidine and x-rays separately. Often fewer aberrations were found after exposure to radiation from both sources than were found after exposure to x-rays alone. At the same fixation times, nonradioactive thymidine did not affect the yield of x-ray-induced aberrations. The same phenomenon occurred at earlier fixation times, after exposure to 30 or 40 rad of x-rays and [3H]thymidine. This response is analogous to the adaptive response to alkylating agents whereby prior treatment with small doses for a long period reduces the damage occurring from large doses of similar agents given for a short time.

The distribution of chromosomal aberrations between and within chromosomes of male D, melanogaster somatic cells after treatment with UV has been analyzed. -- Distribution of the breaks between chromosomes was largely nonrandom since we found a higher aberration frequency than that expected on the Y chromosome. Moreover, within the chromosomes the aberrations are clustered in the pericentromeric heterochromatic regions. The above distribution is compared with that of the breaks induced by X rays and methyl-methane-sulphonate (MMS) which were distributed in a different pattern.

The relative frequencies of X-ray-induced symmetrical and asymmetrical chromatid interchanges were analysed as a function of the cell cycle in somatic cells of Drosophila melanogaster. In exchanges between autosomes, during the S phase, a clear prevalence of asymmetrical rejoining was observed. Later, this prevalence became reduced as the cell approached mitosis. On the other hand, in the exchanges between X-chromosomes in the females there were no significant variations in the type of rejoining through the cell cycle, there being a slight but consistent preference for symmetrical rejoining. These data are discussed in relation to the hypothesis proposed by Olivieri et al. [12] on the organization of the chromosomal sub-units in the interphase nucleus.

Neural ganglia of wild type third-instar larvae of Drosophila melanogaster were incubated for 13 hours at various concentrations of BUdR (1, 3, 9, 27 micrograms/ml). Metaphases were collected with colchicine, stained with Hoechst 33258, and scored under a fluorescence microscope. Metaphases in which the sister chromatids were clearly differentiated were scored for the presence of sister-chromatid exchanges (SCEs). At the lowest concentration of BUdR (1 microgram/ml), no SCEs were observed in either male or female neuroblasts. The SCEs were found at the higher concentrations of BUdR (3, 9, And 27 micrograms/ml) and with a greater frequency in females than in males. Therefore SCEs are not a spontaneous phenomenon in D. melanogaster, but are induced by BUdR incorporated in the DNA. A striking nonrandomness was found in the distribution of SCEs along the chromosomes. More than a third of the SCEs were clustered in the junctions between euchromatin and heterochromatin. The remaining SCEs were preferentially localized within the heterochromatic regions of the X chromosome and the autosomes and primarily on the entirely heterochromatic Y chromosome.--In order to find an alternative way of measuring the frequency of SCEs in the Drosophila neuroblasts, the occurrence of double dicentric rings was studied in two stocks carrying monocentric ring-X chromosomes. One ring chromosome, C(1)TR94--2, shows a rate of dicentric ring formation corresponding to the frequency of SCEs observed in the BUdR-labelled rod chromosomes. The other ring studied, R(1)2, exhibits a frequency of SCEs higher than that observed with both C(1) TR94--2 and rod chromosomes.

Human lymphocytes exposed to low doses of ionizing radiations from incorporated tritiated thymidine ([3H]dThd) or from X-rays become less susceptible to the induction of chromatid aberrations by high doses of X-rays. This indicates that low doses of ionizing radiation can produce an effect similar to the adaptive response observed with alkylating agents in prokaryotes, animal and plant cells. To determine whether there is individual variability in the adaptive response to ionizing radiations we exposed human lymphocytes from 18 different healthy donors to 'adapting' doses of [3H]dThd (0.01 microCi/ml) or X-rays (0.01 Gy) and subsequently to a 'challenge' treatment of 0.75 Gy of X-rays delivered 2 h before fixation. Four of the 18 donors did not show an adaptive response; in some cases in these individuals a synergistic response of increased, rather than decreased, damage was found. Two of these 4 donors showed no adaptive response in 3 subsequent experiments separated by 4-month intervals. This suggests that the human population exhibits a heterogeneity in the adaptive response to ionizing radiations which might be, at least in part, genetically determined.

Experiments were carried out using human lymphocytes from a male donor in order to test the action of 5-azaC treatment on the induction of SCE and chromatid aberrations. The 5-azaC was found to increase the frequency of both baseline and MMC-induced SCEs. Using the same 5-azaC treatment conditions it was found that the frequency of X-ray-induced CA did not increase.

A technique has been perfected for enabling good microscope preparations to be obtained from the larval ganglia of Drosophila melanogaster. This system was then tested with X-rays and an extensive series of data was obtained on the chromosome aberrations induced in the various stages of the cell cycle.-The analysis of the results obtained offers the following points of interest: (1) There exists a difference in radio-sensitivity between the two sexes. The females constantly display a greater frequency of both chromosome and chromatid aberrations. They also display a greater frequency of spontaneous aberrations. (2) In both sexes the overall chromosome damage is greater in cells irradiated in stages G(2) and G(1). These two peaks of greater radiosensitivity are produced by a high frequency of terminal deletions and chromatid exchanges and by a high frequency of dicentrics, respectively. (3) The aberrations are not distributed at random among the various chromosomes. On the average, the Y chromosome is found to be more resistant and the breaks are preferentially localized in the pericentromeric heterochromatin of the X chromosome and of the autosomes. (4) Somatic pairing influences the frequency and type of the chromosome aberrations induced. In this system, such an arrangement of the chromosomes results in a high frequency of exchanges and dicentrics between homologous chromosomes and a low frequency of scorable translocations. Moreover, somatic pairing, probably by preventing the formation of looped regions in the interphase chromosomes, results in the almost total absence of intrachanges at both chromosome and chromatid level.