Alkylation of DNA in F344 rat thymus following administration of 1-n-propyl-1-nitrosourea in vivo and comparison of O6-alkylguanine DNA alkyltransferase activity in thymus from F344 and Long-Evans rats in vitro.
The tissue distribution of radioactivity 1 h after i.p. injection of [n-propyl-2,3-3H]1-n-propyl-1-nitrosourea (PNU) (100 mg/kg) was studied in male F344 rats. This treatment results in a high incidence of thymic lymphomas. The 3H concentration in the thymus, testis and brain was significantly higher than that in blood. 7-n-propylguanine and O6-n-propylguanine were detected in thymus DNA of F344 rats treated with PNU; the ratio of O6-n-propylguanine/7-n-propylguanine was 0.35, lower than following DNA alkylation in vitro. This suggests the presence of O6-alkylguanine DNA alkyltransferase (AGT) in thymus. AGT activity in F344 and Long-Evans rats was compared by using a 3H-propylated DNA as a substrate. AGT activity in the thymus of F344 rats was lower than that in the liver. The AGT activity in the thymus of Long-Evans strain, which had a low incidence of PNU-induced thymic lymphomas, was higher than that of F344 strain. The high level of DNA alkylation by PNU and the low activity of AGT in the thymus may contribute to the high incidence of thymic lymphoma in F344 rat.
Morimoto
K
K
Division of Medical Chemistry, National Institute of Hygienic Sciences, Tokyo, Japan.
Tanaka
A
A
Yamaha
T
T
Takahashi
A
A
D000478:Alkylation; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D066298:In Vitro Techniques; D008223:Lymphoma / Q000139:chemically induced; D008297:Male; D008780:Methyltransferases / Q000032:analysis*; D009607:Nitrosourea Compounds / Q000378:metabolism* / Q000633:toxicity; D019853:O(6)-Methylguanine-DNA Methyltransferase; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013950:Thymus Gland / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000139:chemically induced; D014018:Tissue Distribution
D002273:Carcinogens; D009607:Nitrosourea Compounds; C020796:propylnitrosourea; D004247:DNA; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase