Age-related alterations in 32P-postlabeled DNA adducts in livers of mice infected with the tumorigenic bacterial pathogen, Helicobacter hepaticus.
Helicobacter hepaticus causes chronic active hepatitis and liver tumors in mice, with associated increase in reactive oxygen species. Indigenous (I)-compounds are bulky DNA adducts present at low levels and detected by 32P-post-labeling. Some may be caused by reactive oxygen species; others occur normally and decrease during liver tumorigenesis. The identity of most is unknown. We investigated whether mouse liver infection by H. hepaticus and resulting progression of hepatic lesions would be associated with qualitative or quantitative changes in I-compounds. Mice were 3, 6, 9, and 12 months of age; liver disease ranged from minimal through marked. In control A/J mice, up to 20 I-compounds were detected, and the total level of these did not change with age, whereas 11 individual I-compounds showed marked age-related differences. These appeared to be coordinately regulated, as the total of these 11 adducts was constant at 6-12 months. In A/JNCr mice naturally infected with H. hepaticus, up to 12 hepatic I-compounds were found. Total levels varied markedly with age and were high at 6 and 12 months. Neither total adduct levels, nor the amount of any individual adduct, correlated positively with severity of hepatic lesions; in some cases, highest levels were found in livers with least disease. Thus, liver infection and tumorigenesis by H. hepaticus was not associated with an increase in any 32P-postlabeled DNA adduct. Marked, and distinct, age-related changes in total or individual adducts in control and infected mice suggest a role in the physiological alterations of aging and in host response to infection.
Josyula
S
S
Department of Pathology, Medical College of Ohio, Toledo, OH, USA.
Schut
H A
HA
Diwan
B A
BA
Anver
M R
MR
Anderson
L M
LM
D000375:Aging; D000818:Animals; D002855:Chromatography, Thin Layer; D004247:DNA / Q000235:genetics / Q000378:metabolism; D018736:DNA Adducts / Q000032:analysis*; D016998:Helicobacter; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology*; D008099:Liver / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010761:Phosphorus Radioisotopes
D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D004247:DNA