Change of polyamine content in mouse skin by leupeptin, a protease inhibitor, during early stage of tumorigenesis.
The effect of a microbial protease inhibitor, leupeptin, on the content of polyamine in the mouse skin was examined during the early stage of tumorigenesis induced by a single application of 7,12-dimethylbenz[a]anthracene (DMBA) and repeated application of croton oil thereafter. Polyamine content in the skin was measured at 3, 5, 7, and 9 weeks during tumorigenesis. The mice with no visible tumor were selected for measurement of polyamine content at 9 weeks. Mice were left untreated for at least 1 week before measurement of polyamine. Polyamine in the skin was extracted with ice-cold 0.4N HClO4 and separated into putrescine, spermidine, and spermine fractions through CM-cellulose column. Polyamine concentration was determined by fluorometry with fluorescamine. Group A mice painted with croton oil 3 times a week did not develop tumors. Group B mice painted with a single DMBA developed skin tumors, and group C mice painted with a single DMBA and croton oil 3 times a week showed higher development of skin tumors than group B. Group D mice treated as group C and then painted with leupeptin about 2 hr after croton oil treatment. Animals in groups B, C, and D had higher spermidine content as group A at 3 and 5 weeks. Content of spermidine in group B decreased at 7 and 9 weeks compared with group C which had a high content throughout the time tested. Leupeptin treatment in group D inhibited spermidine content in the skin after 7 weeks without affecting until 5 weeks.
D000818:Animals; D001551:Benz(a)Anthracenes; D003436:Croton Oil; D007976:Leupeptins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D011073:Polyamines / Q000032:analysis*; D012867:Skin / Q000032:analysis*; D012878:Skin Neoplasms / Q000032:analysis* / Q000139:chemically induced; D013095:Spermidine / Q000032:analysis; D013096:Spermine / Q000032:analysis
D001551:Benz(a)Anthracenes; D007976:Leupeptins; D009842:Oligopeptides; D011073:Polyamines; D013096:Spermine; D003436:Croton Oil; D013095:Spermidine