With respect to clinical signs of the radiation syndromes, some remarkable species variations exist. For example the marked delayed reaction of the acute hematologic response in cows. An unusually high sensitivity of the central nervous system is found in burros, which is probably caused by acute vascular and/or metabolic changes in the brain. The species-specific number of intestinal crypt and hemopoietic stem cells may explain the early survival differences among species after high doses of irradiation. Mortality due to acute radiation syndromes is lowest in chickens. Regarding late effects, various neoplasms are typical in dogs, and cattle more commonly develop cataracts.

Acute Disease↗

PubMedDate not supplied

O6-alkylguanine-DNA alkyltransferase in the chick embryo during development.

In the whole embryo, O6-alkylguanine-DNA alkyltransferase (AT) activity increased until day 9 of development and declined sharply after day 13. AT activity of the liver was greatest between day 12 and day 20 and decreased fast after hatching. In the brain, AT activities reached a maximum at day 17 and 18 and declined sharply after hatching. At two developmental stages with different AT activities (day 10 and day 17) DNA alkylation in the brains was estimated 6, 12, 24 and 48 h after administration of N-methyl-N-nitrosourea in ovo by viscometric measurement of DNA fragmentation. The high AT activities of the chicken embryo brain at the 17th day of development correlated with minor DNA fragmentation following a repair period of 12-24 h. It is suggested that the high basal level of AT in the chick embryo might have a protective function against the persistence of the genotoxic lesion O6-methylguanine during development.

Aging↗

PubMedDate not supplied

RNA metabolism, DNA damage and cellular resistance to X-rays: investigations in chick embryo and rat cells.

Three hours after X-irradiation in vivo with 8 Gy the in vitro incorporation of [3H]uridine into total RNA of liver(L)- and brain(B)-cells of the chick embryo was reduced to 77% and 90%, respectively; the mRNA fraction was strongest inhibited. Under the same conditions, protein synthesis of L-cells declined to 62%, while protein synthesis of B-cells was not influenced. RNA and protein metabolism was not altered following X-irradiation in vitro (1.75-56 Gy). Compared to thymic- and splenic cells of the rat, chicken embryo cells exhibited higher constitutive poly(adenosine diphosphate-ribose)polymerase activity and lower X-irradiation-induced DNA damage. Whereas the slight inhibition of RNA and protein synthesis by X-irradiation in ovo may be an abscopal and/or secondary phenomenon reflecting DNA and/or cellular damage, the present investigations comprising various cell types argue for an efficient DNA repair in chicken embryo cells caused, at least partly, by a high constitutive activity of DNA repair proteins.

Animals↗

PubMedDate not supplied

Differences between thymic and splenic cells of the rat: biochemical and physico-chemical investigations in vitro on DNA topoisomerase II--inhibitors and thiyl radicals.

Interactions of novobiocin (NB) and nalidixic acid (NA) with thiols were investigated in vitro in thymic (T-) and splenic (S-) cells of the rat, by determining nucleic acid synthesis as well as nucleoid sedimentation and viscosity of alkaline cell lysates. In T-cells NB, at concentrations of 0.35-1.4 mM, increased unscheduled DNA synthesis (UDS) and RNA synthesis (RNS), whereas S-cells underwent a dose-dependent inhibition of UDS and RNS following exposure to NB at concentrations > 0.7 mM. Combining NA and thiols (e.g., dithiothreitol) resulted in a slight stimulation of UDS in S-cells and in a highly significant increase of UDS in T-cells ascribed to a depletion of the cellular thymidine pool. In both cell types, neither NB nor NA exerted a significant effect on thiol-induced DNA damage. At a concentration of 1.4 mM, NB increased the viscosity of alkaline T-cell lysates; the opposite effect was observed in S-cells. From these results as well as from previous investigations we conclude that T- and S-cells differ in their state of chromatin conformation. This interpretation offers a simple model for the study of the influence of chromatin structure on cell-specific physico-and/or chemico-biological interactions.

Animals↗

PubMedDate not supplied

Radioadapted chicken embryo cells: challenge specificity and alterations in higher-order DNA structure.

Radioadapted chicken embryo cells (X-irradiation in ovo with 10 cGy at the 14th day of development with priming periods of 24 h) were treated in vitro by challenge doses of 14 different DNA- and/or chromatin-interactive agents, including X-rays. A decrease in the cellular damage, as measured by scheduled DNA synthesis, was only observed with X-irradiation. Sedimentation of nucleoids as well as viscosity of alkaline lysates from ethidium bromide (0.35-400 micrograms/ml)-, novobiocin (125-1800 micrograms/ml)-, and hyperthermia (30 min at 43 degrees and 45 degrees)-treated cells suggest a higher tendency of radioadapted cells to undergo positive DNA supercoiling. When DNA from adapted and non-adapted chicken embryo cells was used as substrate, neither its digestion by DNase I nor the inhibition of DNase I activity by various DNA-interactive agents was changed in primed cells. From the previous investigations as well as from the present results it is concluded that an increase of tightening of protein-DNA interactions within the nuclear matrix is a molecular determinant of the elevated radiation resistance in radioadapted chicken embryo cells.

Animals↗

PubMedDate not supplied

Caffeine-DNA interactions: biochemical investigations comprising DNA-repair enzymes and nucleic acid synthesis.

Chicken embryo cells were treated with caffeine (0.5-8.0 mM) alone or combined with various chemical and physical DNA-and/or chromatin-interactive agents. Analytical procedures comprised scheduled (SDS) and unscheduled (UDS) DNA synthesis, RNA synthesis (RNS), the activities of O6-alkylguanine-DNA alkyltransferase (AT) and poly (ADP-ribose) polymerase (PARP) as well as nucleoid sedimentation. Additional investigations were done in rat thymic and splenic cells. The effect of caffeine on DNase-I activity served as an in vitro-model system. When present in the PARP-, SDS-, UDS- and RNS-assays, caffeine inhibited the corresponding tracer (14C-NAD, dT-3H, 3H-U) incorporation in a dose-dependent manner. The AT activity was slightly stimulated. At concentrations of 0.06-0.3 mM, caffeine inhibited DNase-I activity by excess substrate. No specific effects of caffeine could be shown by nucleoid sedimentation. Besides the reduced permeability of the cells to nucleic acid precursors, the results obtained with the PARP- and DNase-I assays give evidence for the formation of a DNA-caffeine adduct as a prominent mechanism of cellular caffeine effects including DNA repair inhibition.

ADP Ribose Transferases↗

PubMedDate not supplied

[Interactions of DNA topoisomerase inhibitors novobiocin and nalidixic acid with some cytotoxic agents. In vitro investigations in rat thymic and splenic cells].

Interactions of novobiocin (NB) and/or nalidixic acid (NA) with some cytotoxic agents--UV light (UV), X-rays, methylmethanesulfonate (MMS), bleomycin (BM), adriamycin (AM), cis-diaminedichloroplatinum(II) (CDDP), mitomycin C (MIT), ethidiumbromide (EB), and suramin (SA)--have been investigated in thymic (T) and splenic (S) cells of the rat in vitro by measuring semiconservative (SDS) and unscheduled (UDS) DNA synthesis as well as sedimentation and viscosity of nucleoids. Combining NB (900 micrograms/ml) and/or NA (1800-3600 micrograms/ml) with UV, MMS, BM, AM, MIT, and SA resulted in additive effects on SDS and UDS. Synergistic actions were observed in T- and S-cells simultaneously treated by NB and CDDP, whereas the effects of NB could be antagonized to some extent by EB and vice versa. In X-irradiated (greater than or equal to 28 Gy) cells pretreated by NB (NA), UDS was diminished (T-cells) or enhanced (S-cells). The results are consistent with the following postulates: 1 degree in S-cells, DNA is much more supercoiled than in T-cells but in the opposite sense (positive superhelicity). 2 degrees DNA supercoiling (DNA compactness) is influenced therefore by DNA-topoisomerase inhibitors and intercalating agents in a highly agent- and cell-specific manner.

Animals↗