N-(2-mercaptoethyl)-1,3-diaminopropane (WR1065) protects against radiation-induced cell killing and mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in V79 Chinese hamster lung fibroblast cells. At a concentration of 4 mM, WR1065 was found to be effective in protecting against radiation-induced cell lethality only if present during irradiation, e.g., a dose modification factor (DMF) of 1.9. No protective effect was observed if the protector was added within 5 min after irradiation or 3 h later, e.g., DMFs of 1.0 and 1.1, respectively. The effect of WR1065 on radiation-induced mutation, expressed as resistance to the cytotoxic purine analogue 6-thioguanine (HGPRT), was also investigated. In contrast to the treatment-schedule dependence for protection by WR1065 against cell killing, this agent was effective in reducing radiation-induced mutations regardless of when it was administered. Following a dose of 10 Gy of 60Co gamma-rays, the mutation frequencies observed per 10(6) survivors were 77 +/- 8, 27 +/- 6, 42 +/- 7, and 42 +/- 7 for radiation only, and WR1065 present during, immediately after, or 3 h after irradiation. These data suggest that although a segment of radiation-induced damage leading to reproductive death cannot be modulated through the postirradiation action of WR1065, processes leading to the fixation of gross genetic damage and mutation induction in surviving cells can be effectively altered and interfered with leading to a marked reduction in mutation frequency.
This report details an unusual clinical presentation of anaphylactic shock due to Hymenoptera envenomation in a dog. To the authors' knowledge, spontaneous hemoperitoneum associated with anaphylaxis and bee envenomation has not been documented in the veterinary literature.
Wortmannin has been shown to be an efficient radiosensitizer. Since wortmannin is able to inhibit DNA-dependent protein kinase (DNA-PK) and double-strand break (DSB) rejoining, it is believed that its mechanism of radiation sensitization is through the inhibition of DNA-PK-mediated repair of DSBs. However, since wortmannin is not a specific inhibitor, the possibility that other kinases are inhibited and thereby may contribute to radiosensitization cannot be ruled out. Here we present data confirming the radiosensitizing effect of wortmannin on cells of different cell lines. In the same range of wortmannin concentrations, survival after exposure to ionizing radiation correlated well with DSB rejoining and the induction of micronuclei, suggesting that the inhibition of the processing of DSBs is involved in the sensitizing effect. Pretreatment with wortmannin enhanced the radiosensitivity of ataxia telangiectasia (AT) cells, thereby precluding the participation of ATM protein in the radiation sensitization by wortmannin. At the same time, irradiated DNA-PK-deficient cells were not significantly affected by pretreatment with wortmannin. These observations support a likely mechanism; that is, wortmannin sensitizes cells to radiation through inhibition of the DNA-PK-mediated rejoining of DSBs.
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