The Shape of the Dose–Response Curve for Radiation-Induced Neoplastic TransformationIn Vitro: Evidence for an Adaptive Response against Neoplastic Transformation at Low Doses of Low-LET Radiation

2001 ◽  
Vol 156 (6) ◽  
pp. 700-707 ◽  
Author(s):  
J. L. Redpath ◽  
D. Liang ◽  
T. H. Taylor ◽  
C. Christie ◽  
E. Elmore
Author(s):  
Richard Wakeford ◽  
E. Janet Tawn

Controversy continues over the shape of the dose-response curve describing the risk of stochastic health effects (cancer and hereditary disorders) following exposure to low doses of ionising radiation. Radiological protection is currently based upon the assumption that the dose-response curve has no threshold and is linear in the low dose region. This position is challenged by groups suggesting either that this approach seriously underestimates the true risk at low doses or that low-level exposure results in no risk (a threshold dose exists) or even a beneficial effect (“radiation hormesis”). In this paper, we examine the epidemiological and radiobiological bases of the linear no-threshold model and some of the alternatives that have been proposed. We conclude that the evidence for a material deviation from a linear no-threshold dose-response relationship at low doses is not persuasive and that the standard model provides the most parsimonious description of the available scientific evidence.


1998 ◽  
Vol 17 (5) ◽  
pp. 254-258 ◽  
Author(s):  
Justin G Teeguarden ◽  
Yvonne P Dragan ◽  
Henry C Pitot

Hormesis has been defined as a dose-response relationship which depicts improvement in some endpoint (increased metabolic rates, reduction in tumor incidence, etc.) at low doses of a toxic compound followed by a decline in the endpoint at higher doses. The existence of hormetic responses to carcinogenic agents has several implications for the bioassay and hazard assessment of carcinogens. To be capable of detecting and statistically testing for hormetic or other nonlinear dose-response functions, current study designs must be modified to include lower doses and sufficiently large numbers of animals. In addition, improved statistical methods for testing nonlinear dose-response relationships will have to be developed. Research integrating physiologically-based pharmacokinetic model descriptions of target dose with mechanistic data holds the greatest promise for improving the description of the dose-response curve at low doses. The 1996 Proposed Carcinogen Risk Assessment Guidelines encourage the use of mechanistic data to improve the descriptions of the dose-response curve at low doses, but do not distinguish between the types of nonlinear dose-response curves. Should this refined approach lead to substantial support for hormesis in carcinogenic processes, future guidelines will need to provide guidance on establishing safe doses and communicating the results to the public.


1987 ◽  
Vol 33 (9) ◽  
pp. 1603-1607 ◽  
Author(s):  
W D Odell ◽  
J Griffin

Abstract We have developed a sensitive, specific, noncompetitive sandwich-type assay for human lutropin (hLH). Two monoclonal antibodies are used, and there is no cross reaction with human choriogonadotropin (hCG) or human follitropin (hFSH), and little or none with human thyrotropin (hTSH). There also is no reaction with the free beta chains of hLH and hCG. The detection limit is less than 0.5 int. units of hLH per liter of serum, and the dose-response curve is linear between 0 and 10 int. units/L. The intra-assay CV averaged 5.4% at low doses of hLH; the interassay CV averaged 12.5%.


1953 ◽  
Vol 6 (2) ◽  
pp. 300 ◽  
Author(s):  
WK Whitten

Treatment of chorionic. gonadotrophin with periodate ions mo<;lified the ,hormone so that it was no longer :inactivated by influenza virus. T1).e. dose response curve of the treated hormone was less steep than for untreated, which precluded any accurate comparison. However, at low doses no loss was detected.


1967 ◽  
Vol 56 (4) ◽  
pp. 619-625 ◽  
Author(s):  
Hans Jacob Koed ◽  
Christian Hamburger

ABSTRACT Comparison of the dose-response curves for LH of ovine origin (NIH-LH-S8) and of human origin (IRP-HMG-2) using the OAAD test showed a small, though statistically significant difference, the dose-response curve for LH of human origin being a little flatter. Two standard curves for ovine LH obtained with 14 months' interval, were parallel but at different levels of ovarian ascorbic acid. When the mean ascorbic acid depletions were calculated as percentages of the control levels, the two curves for NIH-LH-S8 were identical. The use of standards of human origin in the OAAD test for LH activity of human preparations is recommended.


1961 ◽  
Vol 37 (4) ◽  
pp. 565-576 ◽  
Author(s):  
Richard A. Miller

ABSTRACT Four per cent formaldehyde, insulin, or epinephrine in oil was injected for 5 days into pigeons subjected to varying degrees of hypophysectomy alone or together with large lesions in the median eminence and hypothalamus. Adrenals atrophied after the removal of the pars distalis alone or together with the neurohypophysis in untreated pigeons but showed markedly hypertrophic interrenal tissue (cortex in mammals) after treatment with formaldehyde or insulin. The slope of the dose-response curve was similar in operated and unoperated pigeons. The accumulation of bile in the liver parenchyma, which may occur after removal of the pars distalis, is an endogenous stress which was associated regularly with adrenal hypertrophy. After very large lesions of the median eminence and ventral hypothalamus in addition to total hypophysectomy, adrenals hypertrophied rather than atrophied, and the response to formaldehyde paralleled that in intact and »hypohysectomized« pigeons. Interrenal tissue was stimulated regularly; chromaffin tissue was partially degranulated, sometimes showed hyperplasia with colchicine, but only occasionally appeared hypertrophied. Epinephrine in nearly lethal doses caused only minimal adrenal enlargement. After adrenal denervation followed by hypophysectomy, the adrenals were still stimulated by formaldehyde. It appears that the interrenal tissue of the pigeon responds to a humoral stimulus not of hypophyseal origin in the absence of the hypophyseal-hypothalamic system.


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