Mouse and rat strain variations in sensitivity to N-nitroso-diethylamine, hereditary transmission of the trait and the effect of 3-tert-butyl-4-hydroxyanisole on sensitivity.
1. Strain variations among male mice were studied in terms of the number of days of survival with chronic administration of N-nitroso-diethylamine (NDEA). Four inbred strains, two F1 progenies and one F2 progeny were tested. 2. BALB/c mice survived for the longest period, whereas C3H mice survived for the shortest time. Results of examinations of BALB/c-C3H-F1, -F2 and C57BL-CBA-F1 mice revealed that the hereditary trait could be adequately explained by postulating two loci of genes or gene clusters that regulate the sensitivity to NDEA. 3. Simultaneous chronic administration of 3-tert-butyl-4-hydroxyanisole (BHA) could prolong the survival period. 4. Preliminary histopathological examinations of the liver tissues revealed that the lesion at the time of death of the mice varied considerably depending on the strain and the length of survival. Evidence for hereditary transmission of the characteristics of histopathological changes, including development of liver hemangiosarcoma, is presented. 5. The strain variations among male and female rats were also studied in terms of the number of days of survival with chronic administration of NDEA. Five strains and one F1 progeny were tested. 6. From these and previous observations, the possible biochemical factors determining sensitivity to NDEA were discussed.
Horie
S
S
Department of Biochemistry, School of Medicine, Kitasato University, Kanagawa, Japan.
Ohbu
M
M
Okudaira
M
M
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D008099:Liver / Q000201:enzymology / Q000473:pathology; D051379:Mice / Q000235:genetics*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000235:genetics*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats / Q000235:genetics*; D013045:Species Specificity; D015996:Survival Rate; D013997:Time Factors
D016588:Anticarcinogenic Agents; D002083:Butylated Hydroxyanisole; D004052:Diethylnitrosamine; D003577:Cytochrome P-450 Enzyme System; D016660:NAD(P)H Dehydrogenase (Quinone); D010634:Phenobarbital