The formation and repair of @entity900 ( @entity7397 )-induced DNA cross-links in cells from a number of different @entity19 tissues, both normal and neoplastic, were compared in three different populations of animals, @entity5 -free @entity19 and @entity19 bearing a transplanted @entity1492 (either FSa or NFSa) in their thighs. Groups of @entity19 were given i.v. injections of 4-12-mg/kg doses of @entity7397 , and the amount of @entity7397 -induced DNA cross-linking was determined at different times after injection using an adaptation of the alkaline elution technique. The degree of cross-linking in each tissue was linearly related to the dose of @entity7397 at either 6 or 24 h after injection and varied significantly among the different tissues, with FSa, NFSa, kidney, and liver showing the highest level of cross-linking of the tissues studied. The relative contributions of DNA-interstrand and DNA-protein cross-links to the elution profiles were estimated by proteinase K (PK) digestion. At either 6 or 24 h after injection with @entity7397 , the rate of elution of the DNA was substantially increased by PK, indicating a large contribution of DNA-protein cross-links. This effect was observed in all tissues studied, although the proportion of PK-resistant lesions appeared to vary from tissue to tissue, liver and spleen showing a significantly lower proportion of DNA-interstrand to total @entity5 . For liver, virtually no interstrand cross-links could be detected after PK treatment. The kinetics of the repair of @entity7397 -induced DNA cross-linking in these tissues were also compared. In cells from @entity5 -free animals, the amount of total (DNA-interstrand plus DNA-protein) cross-linking increased gradually, reaching a maximum after about 6 h; however, little evidence of repair of these lesions was observed in any of these normal tissues. In fact, the degree of cross-linking tended to increase somewhat between 6 and 24 h after injection. The kinetics of cross-linking in cells isolated from the FSa @entity5 were very different; while there was an initial increase in cross-linking up to 6 h, these lesions were subsequently repaired, although at a somewhat slower rate than has been reported for cultured @entity1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Kinetics of DNA cross-linking in normal and neoplastic @entity19 tissues following treatment with XXXX in vivo.

@entity1 :: ('9606', 'Species') :: ['mammalian'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cross-links than either of the tumors'] @entity900 :: ('MESH:D002945', 'Chemical') :: ['cis-diamminedichloroplatinum(II)'] @entity1492 :: ('MESH:D005354', 'Disease') :: ['fibrosarcoma'] @entity7397 :: ('CHEBI:27899', 'Chemical') :: ['cis-DDP']
@entity900 :: (MESH:D002945,Chemical) :: ['cis-diamminedichloroplatinum(II)']
