N-Methyl-N-Nitrosourea (MNU): A positive control chemical for p53+/- mouse carcinogenicity studies.
This study evaluated the effects of a single intraperitoneal injection of N-methyl-N-nitrosourea (MNU) in citrate buffer (pH 4.5) at a dose of 75 mg/kg in thirty male and thirty female p53+/- mice followed by a six-month observation period. Fifteen control mice per sex received a single intraperitoneal injection of citrate buffer. Fifty-six of sixty mice treated with MNU died or were sacrificed before the end of the observation period. Twenty-four males and twenty-seven females treated with MNU developed malignant lymphoma of the thymus; of these, twenty-three males and twenty-seven females had corresponding enlargement or masses in the thymus at necropsy. Lymphoblasts in thymic lymphomas stained positively for mouse CD3 antigen, indicating a T-cell lineage. One control female mouse had malignant lymphoma of the spleen that did not involve the thymus. Nine males and five females treated with MNU had adenomas or adenocarcinomas of the small intestine, whereas no intestinal neoplasms were observed in control mice. These findings support the use of a single dose of MNU as a positive control chemical in six-month p53+/- mouse carcinogenicity studies and suggest that examination of the thymus alone is sufficient to evaluate the validity of the model system.
Morton
Daniel
D
Pfizer, Groton, Connecticut 06340, USA. dan.g.morton@pfizer.com
Bailey
Keith L
KL
Stout
Cheryl L
CL
Weaver
R John
RJ
White
Kathleen A
KA
Lorenzen
Marianne J
MJ
Ball
Douglas J
DJ
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D015197:Carcinogenicity Tests / Q000379:methods*; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004379:Duodenal Neoplasms / Q000139:chemically induced / Q000473:pathology; D005260:Female; D016158:Genes, p53; D006579:Heterozygote; D007274:Injections, Intraperitoneal; D007421:Intestine, Small / Q000473:pathology; D007580:Jejunal Neoplasms / Q000139:chemically induced / Q000473:pathology; D008223:Lymphoma / Q000139:chemically induced / Q000473:pathology; D008297:Male; D008770:Methylnitrosourea / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000139:chemically induced* / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology; D013953:Thymus Neoplasms / Q000139:chemically induced / Q000473:pathology
D017252:CD3 Complex; D002273:Carcinogens; D008770:Methylnitrosourea