Thymomas Induced by Simple Alkylating Agents in C57BL/Cbi Mice: Kinetics of the Dose Response23

1980 ◽  
Keyword(s):  
Dose Response ◽  
Alkylating Agents ◽  
Kinetics Of

Kinetics of DNA Repair Under Chronic Irradiation at Low and Medium Dose Rates in Repair Proficient and Repair Compromised Normal Fibroblasts

2021 ◽  
Author(s):  
Elena K. Zaharieva ◽  
Megumi Sasatani ◽  
Kenji Kamiya
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dose Rate ◽  
Dose Response ◽  
Chronic Irradiation ◽  
Dose Rates ◽  
Chronic Radiation ◽  
Damage Repair ◽  
Kinetics Of ◽  
Medium Dose

We present time and dose dependencies for the formation of 53BP1 and γH2AX DNA damage repair foci after chronic radiation exposure at dose rates of 140, 250 and 450 mGy/day from 3 to 96 h, in human and mouse repair proficient and ATM or DNA-PK deficient repair compromised cell models. We describe the time/dose-response curves using a mathematical equation which contains a linear component for the induction of DNA damage repair foci after irradiation, and an exponential component for their resolution. We show that under conditions of chronic irradiation at low and medium dose rates, the processes of DNA double-strand breaks (DSBs) induction and repair establish an equilibrium, which in repair proficient cells manifests as a plateau-shaped dose-response where the plateau is reached within the first 24 h postirradiation, and its height is proportionate to the radiation dose rate. In contrast, in repair compromised cells, where the rate of repair may be exceeded by the DSB induction rate, DNA damage accumulates with time of exposure and total absorbed dose. In addition, we discuss the biological meaning of the observed dependencies by presenting the frequency of micronuclei formation under the same irradiation conditions as a marker of radiation-induced genomic instability. We believe that the data and analysis presented here shed light on the kinetics of DNA repair under chronic radiation and are useful for future studies in the low-to-medium dose rate range.

scholarly journals Chemotherapy and Risk of Subsequent Malignant Neoplasms in the Childhood Cancer Survivor Study Cohort

2019 ◽  
Vol 37 (34) ◽  
pp. 3310-3319 ◽  
Author(s):  
Lucie M. Turcotte ◽  
Qi Liu ◽  
Yutaka Yasui ◽  
Tara O. Henderson ◽  
Todd M. Gibson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Childhood Cancer ◽  
Cancer Survivor ◽  
Dose Response ◽  
Cumulative Incidence ◽  
Alkylating Agents ◽  
Childhood Cancer Survivor ◽  
Malignant Neoplasms ◽  
Linear Dose ◽  
Childhood Cancer Survivor Study

PURPOSE Therapeutic radiation in childhood cancer has decreased over time with a concomitant increase in chemotherapy. Limited data exist on chemotherapy-associated subsequent malignant neoplasm (SMN) risk. PATIENTS AND METHODS SMNs occurring > 5 years from diagnosis, excluding nonmelanoma skin cancers, were evaluated in survivors diagnosed when they were < 21 years old, from 1970 to 1999 in the Childhood Cancer Survivor Study (median age at diagnosis, 7.0 years; median age at last follow-up, 31.8 years). Thirty-year SMN cumulative incidence and standardized incidence ratios (SIRs) were estimated by treatment: chemotherapy-only (n = 7,448), chemotherapy plus radiation (n = 10,485), radiation only (n = 2,063), or neither (n = 2,158). Multivariable models were used to assess chemotherapy-associated SMN risk, including dose-response relationships. RESULTS Of 1,498 SMNs among 1,344 survivors, 229 occurred among 206 survivors treated with chemotherapy only. Thirty-year SMN cumulative incidence was 3.9%, 9.0%, 10.8%, and 3.4% for the chemotherapy-only, chemotherapy plus radiation, radiation-only, or neither-treatment groups, respectively. Chemotherapy-only survivors had a 2.8-fold increased SMN risk compared with the general population (95% CI, 2.5 to 3.2), with SIRs increased for subsequent leukemia/lymphoma (1.9; 95% CI, 1.3 to 2.7), breast cancer (4.6; 95% CI, 3.5 to 6.0), soft-tissue sarcoma (3.4; 95% CI, 1.9 to 5.7), thyroid cancer (3.8; 95% CI, 2.7 to 5.1), and melanoma (2.3; 95% CI, 1.5 to 3.5). SMN rate was associated with > 750 mg/m2 platinum (relative rate [RR] 2.7; 95% CI, 1.1 to 6.5), and a dose response was observed between alkylating agents and SMN rate (RR, 1.2/5,000 mg/m2; 95% CI, 1.1 to 1.3). A linear dose response was also demonstrated between anthracyclines and breast cancer rate (RR, 1.3/100 mg/m2; 95% CI, 1.2 to 1.6). CONCLUSION Childhood cancer survivors treated with chemotherapy only, particularly higher cumulative doses of platinum and alkylating agents, face increased SMN risk. Linear dose responses were seen between alkylating agents and SMN rates and between anthracyclines and breast cancer rates. Limiting cumulative doses and consideration of alternate chemotherapies may reduce SMN risk.

Dose response and kinetics of foci disappearance following exposure to high- and low-LET ionizing radiation

2009 ◽  
Vol 85 (10) ◽  
pp. 872-882 ◽  
Author(s):  
Rasa Ugenskiene ◽  
Kevin Prise ◽  
Melvyn Folkard ◽  
Janusz Lekki ◽  
Zbigniew Stachura ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Dose Response ◽  
Kinetics Of

Kinetics of edema formation in rats as influenced by critical doses of dextran

1960 ◽  
Vol 199 (4) ◽  
pp. 657-660 ◽  
Author(s):  
L. Kátó ◽  
B. Gözsy
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Edema Formation ◽  
Critical Dose ◽  
Small Doses ◽  
Full Intensity ◽  
Kinetics Of

The severity and time of edema formation is characteristically influenced by doses of dextran if injected intravenously into rats. The dose-response curve revealed that small doses of dextrans (0.1–0.8 mg/100 gm) provoke maximal edema formation within 10 minutes, while increasing doses produce less severe edema and delay in its appearance, until a critical dose is arrived at, which provokes no hyperemia and no edema at all. Further increase in dose provokes edema again. The critical dose is relatively sharp and characteristic for each type of dextrans. If antihistamines are injected simultaneously with the critical dose, edema appears with full intensity. Experiments suggest that dextrans contain two fractions with opposite effects, one which provokes the edema formation and another which inhibits the response.

scholarly journals The reaction of alkylating agents with bacteriophage R17. Biological effects of phosphotriester formation

1974 ◽  
Vol 137 (2) ◽  
pp. 313-317 ◽  
Author(s):  
Kenneth V. Shooter ◽  
Ruth Howse ◽  
R. Kenneth Merrifield
Keyword(s):  
Reaction Mechanism ◽  
Biological Effects ◽  
Alkylating Agents ◽  
Hydrolysis Reaction ◽  
Ethyl Methanesulphonate ◽  
Neutral Ph ◽  
Rate Of Hydrolysis ◽  
Alkylation Reactions ◽  
Kinetics Of ◽  
Hydrolysis Of

The extent of biological inactivation and of the degradation of the RNA after reaction of bacteriophage R17 with ethyl methanesulphonate, isopropyl methanesulphonate and N-ethyl-N-nitrosourea was studied. Formation of breaks in the RNA chain probably results from hydrolysis of phosphotriesters formed in the alkylation reactions. Near neutral pH the ethyl and isopropyl phosphotriesters are sufficiently stable for the kinetics of the hydrolysis reaction to be followed. Results indicate that the rate of hydrolysis increases rapidly as the pH is raised. The evidence shows that a phosphotriester group does not itself constitute a lethal lesion. The extent of phosphotriester formation by the different agents is discussed in terms of reaction mechanism.

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