The genetic basis of strain-dependent differences in the early phase of radiation injury in mouse lung.
Substantial differences between mouse strains have been reported in the lesions present in the lung during the early phase of radiation injury. Some strains show only classical pneumonitis, while other strains develop substantial fibrosis and hyaline membranes which contribute appreciably to respiratory insufficiency, in addition to pneumonitis. Other strains are intermediate between these extremes. These differences correlate with intrinsic differences in activities of lung plasminogen activator and angiotensin converting enzyme. The genetic basis of these differences was assessed by examining histologically the early reaction in lungs of seven murine hybrids available commercially after whole-thorax irradiation. Crosses between fibrosing and nonfibrosing parents were uniformly nonfibrosing, and crosses between fibrosing and intermediate parents were uniformly intermediate. No evidence of sex linkage was seen. Thus the phenotype in which fibrosis is found is controlled by autosomal recessive determinants. Strains prone to radiation-induced pulmonary fibrosis and hyaline membranes exhibited intrinsically lower activities of lung plasminogen activator and angiotensin converting enzyme than either the nonfibrosing strains or the nonfibrosing hybrid crosses. The median time of death of the hybrids was genetically determined primarily by the longest-lived parent regardless of the types of lesions expressed.
Franko
A J
AJ
Radiobiology, Cross Cancer Institute, Edmonton, Alberta, Canada.
Sharplin
J
J
Ward
W F
WF
Hinz
J M
JM
D000818:Animals; D005260:Female; D005355:Fibrosis; D008168:Lung / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D013045:Species Specificity
D007703:Peptidyl-Dipeptidase A; D010960:Plasminogen Activators