324. Int J Radiat Oncol Biol Phys. 2000 Dec 1;48(5):1539-48.
In-field and out-of-field effects in partial volume lung irradiation in rodents:
possible correlation between early dna damage and functional endpoints.
Moiseenko VV(1), Battista JJ, Hill RP, Travis EL, Van Dyk J.
Author information:
(1)London Regional Cancer Centre, University of Western Ontario, London, Ontario,
Canada.
PURPOSE: Recent observations have shown that there are regional variations in
radiation response in mouse lung as measured by functional assays. Furthermore,
there are both in-field and out-of-field effects in radiation-induced lung damage
as observed by DNA assay in rats. The purpose of this work is: (a) to examine
mice lethality data following partial volume lung irradiation to assess the
possibility of directional or regional effects, (b) to evaluate the correlation
between mice lethality data and DNA damage assayed by micronuclei production in
rat lung, and (c) to re-interpret mice lethality considering the existence of
directional effects in lung cellular response to partial volume irradiation.
METHODS AND MATERIALS: The lethality data for mice, generated at the M. D.
Anderson Cancer Center, Houston, and micronuclei yield data for rats obtained at
Princess Margaret Hospital, Toronto, were used. A radiobiological model that
allows for out-of-field and in-field effects for lung cell damage and lung
response was developed. This model is based on the observation of DNA damage in
shielded parts of rat lung that was assumed relevant to cell lethality and
consequently overall lung response.
RESULTS: While the experimental data indicated directional or regional volume
effects, the applicability of dose and volume as sole predictors of lung response
to radiation was found to be unreliable for lower lung (base) irradiation in
mice. This conforms well to rat lung response where micronuclei were observed in
shielded apical parts of lung following base irradiation. The radiobiological
model, which was specifically developed to account for the lung response outside
of primary irradiated volume, provides a good fit to mice lethality data, using
parameters inferred from rat micronuclei data.
CONCLUSION: Response to lung irradiation in rodents, in particular, elevated
sensitivity to base irradiation, can be interpreted with a hypothesis of in-field
and out-of-field effects for cellular response. If the existence of these effects
for lung is subsequently proven in humans, it will require the incorporation of
geometrical and directional information in normal tissue complication probability
calculations for lung. These considerations are ignored in present approaches
based only on conventional dose-volume histograms.
PMID: 11121660 [PubMed - indexed for MEDLINE]
324. Int J Radiat Oncol Biol Phys. 2000 Dec 1;48(5):1539-48.In-field and out-of-field effects in partial volume lung irradiation in rodents: possible correlation between early dna damage and functional endpoints.Moiseenko VV(1), Battista JJ, Hill RP, Travis EL, Van Dyk J.Author information: (1)London Regional Cancer Centre, University of Western Ontario, London, Ontario,Canada.PURPOSE: Recent observations have shown that there are regional variations inradiation response in mouse lung as measured by functional assays. Furthermore,there are both in-field and out-of-field effects in radiation-induced lung damageas observed by DNA assay in rats. The purpose of this work is: (a) to examinemice lethality data following partial volume lung irradiation to assess thepossibility of directional or regional effects, (b) to evaluate the correlationbetween mice lethality data and DNA damage assayed by micronuclei production inrat lung, and (c) to re-interpret mice lethality considering the existence ofdirectional effects in lung cellular response to partial volume irradiation.METHODS AND MATERIALS: The lethality data for mice, generated at the M. D.Anderson Cancer Center, Houston, and micronuclei yield data for rats obtained at Princess Margaret Hospital, Toronto, were used. A radiobiological model thatallows for out-of-field and in-field effects for lung cell damage and lungresponse was developed. This model is based on the observation of DNA damage inshielded parts of rat lung that was assumed relevant to cell lethality andconsequently overall lung response.RESULTS: While the experimental data indicated directional or regional volumeeffects, the applicability of dose and volume as sole predictors of lung responseto radiation was found to be unreliable for lower lung (base) irradiation inmice. This conforms well to rat lung response where micronuclei were observed in shielded apical parts of lung following base irradiation. The radiobiologicalmodel, which was specifically developed to account for the lung response outside of primary irradiated volume, provides a good fit to mice lethality data, usingparameters inferred from rat micronuclei data.CONCLUSION: Response to lung irradiation in rodents, in particular, elevatedsensitivity to base irradiation, can be interpreted with a hypothesis of in-fieldand out-of-field effects for cellular response. If the existence of these effectsfor lung is subsequently proven in humans, it will require the incorporation ofgeometrical and directional information in normal tissue complication probabilitycalculations for lung. These considerations are ignored in present approachesbased only on conventional dose-volume histograms.PMID: 11121660 [PubMed - indexed for MEDLINE]
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