Induction of minisatellite DNA rearrangements by genotoxic carcinogens in mouse liver tumors.
We investigated whether somatic rearrangements in minisatellite DNA are more frequent in chemically induced mouse liver tumors than they are in spontaneous tumors. CD-1 mouse liver tumors were induced by either a single dose or 15 consecutive daily doses of 7,12-dimethylbenz[alpha]anthracene, 4-aminoazobenzene, N-hydroxy-2-acetyl-aminofluorene or diethylnitrosoamine (DEN). Using DNA fingerprinting analysis, we found that the single- and multiple-dose carcinogen treatments caused a 2- to 5-fold higher frequency of minisatellite DNA rearrangements compared with that found in spontaneous tumors--with the exception of single-dose DEN tumors, which showed no increase in rearrangements. Our results suggest that DNA fingerprinting may be a valuable assay for differentiating certain chemically induced tumors from spontaneous tumors.
Ledwith
B J
BJ
Department of Safety Assessment, Merck Research Laboratories, West Point, PA 19486, USA.
Joslyn
D J
DJ
Troilo
P
P
Leander
K R
KR
Clair
J H
JH
Soper
K A
KA
Manam
S
S
Prahalada
S
S
van Zwieten
M J
MJ
Nichols
W W
WW
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000236:Adenoma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002277:Carcinoma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016172:DNA Fingerprinting; D004273:DNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism; D004276:DNA, Satellite / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D004052:Diethylnitrosamine / Q000633:toxicity; D006881:Hydroxyacetylaminofluorene / Q000633:toxicity; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D010128:p-Aminoazobenzene / Q000633:toxicity
D002273:Carcinogens; D004273:DNA, Neoplasm; D004276:DNA, Satellite; D004052:Diethylnitrosamine; D006881:Hydroxyacetylaminofluorene; D015127:9,10-Dimethyl-1,2-benzanthracene; D010128:p-Aminoazobenzene