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Biomedical subjects

T M Koval

Publications and source records attributed to T M Koval.

32 records · Page 2Linked to original sources
PubMed1986

Enhanced survival by photoreactivation and liquid holding following UV damage of TN-368 insect cells.

These studies demonstrate that the TN-368 lepidopteran insect cell line, which is extremely resistant to the lethal effects of ionizing radiation, is also quite resistant to 254-nm ultraviolet light. While resistance to ionizing radiation in TN-368 cells has been associated with superior DNA repair processes, previous findings have indicated no correlation between survival ability and amount of unscheduled DNA synthesis in response to ultraviolet light. The present studies were undertaken to define the TN-368 ultraviolet light survival response, the ability of the cells to repair UV-induced damage by photoreactivation, the capacity of the cells to undergo UV repair during liquid holding in the dark, and the relationship between photoreactivation and liquid-holding recovery. Survival was assayed by colony formation. 254-nm irradiations were performed using germicidal lamps and photoreactivation was accomplished using black lights. Photoreactivable sectors of UV damage at 50 and 10% survival are 0.65 and 0.68, respectively. Survival responses, both with and without photoreactivation, have a small initial shoulder followed by an exponential region, and finally the curves continue to decrease but with decreasing slope. F0, Fq, and extrapolation number for the exponential portion of the curves are 77.5 J/m2, 16.8 J/m2, and 1.7 for non-photoreactivated cells and 234 J/m2, 56.1 J/m2, and 1.7 for those exposed to photoreactivating light. In the primarily exponential survival region, the fluences required to produce equivalent levels of survival in photoreactivated cells range from approximately 10.8 to 23.3 times as great as cells receiving UV light alone. The maximum survival enhancement of cells maintained under liquid-holding conditions over cells plated immediately following 100-400 J/m2 irradiations appears to be about 2-fold and occurs at 3-6 h of holding. Photoreactivation alone has a greater enhancement of survival than when photoreactivation follows liquid holding, but when liquid holding follows photoreactivation, the enhancement surpasses that of photoreactivation alone.

Animals↗
PubMed1985

Relationship between cell survival and heat-stress protein synthesis in a Drosophila cell line.

Heat-stress protein (hsp) kinetics and clonogenic survival were studied at 33, 37 and 42 degrees C in a continuous Drosophila cell line, WR69-DM-1. Induction and repression of hsp were temperature-dependent and independently modulated. The subsequent cell-survival curves were complex; however, survival generally decreased in a time- and temperature-dependent manner during continuous heating at 33, 37 or 42 degrees C. Constant 33 degrees C heating induced five hsp at 90, 72, 70, 24 and 19 kilodaltons (kDa). A 30 min 33 degrees C heat dose led to thermotolerance after 1, 3 or 6 h incubations at 28 degrees C. The hsp synthesized after this dose were quickly repressed, suggesting the cells were able to respond to this stress. Increasing the challenge temperature to 37 degrees C induced three additional hsp at 34, 22 and 14 kDa, but hsp synthesis did not lead to thermotolerance over the 6 h interval. The number and intensity of hsp synthesized was higher and repression was much slower than at 33 degrees C. Heating at 42 degrees C inhibited all protein synthesis, and thermotolerance was not observed. Direct survival data are critical to understanding the role and function of hsp in Drosophila thermotolerance since the relevance of information on number and kinetics of hsp synthesis and their subsequent localization is dubious without it.

Animals↗
PubMed1984

Selective inhibition of replicative and repair DNA synthesis in mouse colon following administration of 1,2-dimethylhydrazine.

Early alterations in normal semiconservative and repair DNA synthesis were determined in gastrointestinal tissues of HalCR mice following administration of the colon carcinogen 1,2-dimethylhydrazine (DMH). Following DMH injections of 60 and 200 mg/kg, normal DNA synthesis was rapidly inhibited in all tissues. The greatest depressions were observed in the descending colon, followed closely by the ascending colon. DNA repair was estimated by measuring unscheduled DNA synthesis. No repair was observable in the descending or ascending colon. The esophagus, forestomach, jejunum, and ileum demonstrated significant amounts of DNA repair, while the duodenum and gastric stomach displayed nominal or insignificant amounts of repair. Repair DNA synthesis was inhibited by simultaneous administration of caffeine and DMH. The degree of inhibition of normal replicative DNA synthesis and the amount of repair DNA synthesis in response to DMH treatment correlate closely with the incidence of DMH-induced tumors. Most tumors occur in the descending colon, followed by the ascending colon, and only a few in the duodenum and gastric stomach area. Neoplasms are rarely found in the remainder of the gastrointestinal system.

1,2-Dimethylhydrazine↗
PubMed1984

Multiphasic survival response of a radioresistant lepidopteran insect cell line.

TN-368 lepidopteran insect cells display a multiphasic survival response in both air and nitrogen. In each case the survival curve is characterized by an initial small- shouldered component having a steep slope, a plateau or broad- shouldered region near the 0.1 survival level, and finally a shallow slope component. The D0, Dq, and n values for the initial steep slope component in air and nitrogen are, respectively, 65.7 Gy, 9.0 Gy, and 1.2, and 104.4 Gy, 28.8 Gy, and 1.3. The oxygen enhancement ratio (OER) for this portion of the curve is 1.6. The D0, Dq, and n values for the shallow slope component in air and nitrogen are, respectively, 130.2 Gy,--36.1 Gy, and 0.8, and 226.8 Gy, 121.0 Gy, and 1.7. The OER for this portion of the curve is 1.7. The D0 values for each slope and the width of the plateau region all increase proportionally for the nitrogen curve over that of air, the OER being approximately the same for both curve components. A similar multiphasic response was observed at dose rates of 202, 49.6, and 9.1 Gy/min. In addition, the survival of cells which had previously been irradiated with a dose well into the logarithmic region of the more resistant shallow slope portion of the curve retained a multiphasic response. Although cell cycle variations in radiosensitivity may contribute slightly to the response, an inducible or activated repair process would be consistent with the results.

Animals↗
PubMed1983

Intrinsic resistance to the lethal effects of x-irradiation in insect and arachnid cells.

Twelve cell lines representing 10 genera of three orders (Diptera, Lepidoptera, and Orthoptera) of the class Insecta and one cell line (Acarina) from the class Arachnida were examined to discern their sensitivity to the lethal effects of x-irradiation. Radiosensitivity was measured by a combination of colony formation and population growth curve techniques. Each of these arthropod cell lines is significantly more radioresistant than mammalian cells, though the degree of resistance varies greatly with order. Dipteran cells are 3 to 9 times and lepidopteran cells 52 to 104 times more radioresistant than mammalian cells. Orthopteran and acarine cells are intermediate in radiosensitivity between dipteran and lepidopteran cells. These cells, especially the lepidopteran, should be valuable in determining the molecular nature of repair mechanisms that result in resistance to ionizing radiation.

Journal Article↗
PubMed1981

Potentiating effect of benzo[a]pyrene and caffeine on Friend viral leukemogenesis.

The effect of exposing mice to both a chemical carcinogen and leukemia virus with and without an inhibitor of DNA repair were compared. The data indicated that benzo[a]pyrene (BP) could exert a potentiating effect of Friend viral leukemogenesis in mice, which was dependent on the relative times of administration of the chemical and virus. The addition of caffeine as an inhibitor of DNA repair further enhanced the potentiating effect of BP on the leukemia, but in the absence of BP, caffeine showed no carcinogenic effect either when given alone or in conjunction with Friend leukemia virus.

Animals↗
PubMed1977

A comparison of survival and repair of UV-induced DNA damage in cultured insect versus mammalian cells.

Survival and unscheduled DNA synthesis (UDS) were measured in a cultured insect cell line, TN-368, and a cultured mammalian cell line, V-79-4, following exposure to several fluences of ultraviolet light. TN-368 cells were approximately seven times more resistant to the lethal effects of UV than V-79 cells, as determined by colony formation. The amount of UDS per unit amount of DNA is about the same in both cell types 4 hr after 10-50 J/m2 UV irradiations.

Animals↗