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# Relative Resistance to Methotrexate by Proliferating Normal Rabbit Epidermal Cells In vitro

Robert A. Harper and B. Allen Flaxman
In Vitro
Vol. 17, No. 5 (May, 1981), pp. 393-396
Stable URL: http://www.jstor.org/stable/4292515
Page Count: 4
Primary cell cultures of normal rabbit epidermal cells (keratinocytes) were established without the use of enzymatic techniques. Six experiments were carried out on cells from six different rabbits. When these cells were exposed to methotrexate (MTX) for 24 h at $1 \mu g/ml$, proliferation, as measured by cells entering mitosis, was significantly inhibited (P < 0.05) in only one experiment. When the dose of MTX was elevated to $100 \mu g/ml$, only two experiments showed significant inhibition of mitosis. This minimal inhibition of mitosis by MTX was contrasted by the dramatic inhibitory effect of this antimetabolite on DNA synthesis. At $1 \mu g/ml$ MTX for 24 h, DNA synthesis, as measured by $\lbrack ^3H\rbrack deoxyuridine$ uptake, was inhibited > 95%. We can conclude that under certain conditions, the rabbit keratinocyte may represent a normal cell type that is inherently resistant to the antiproliferative effects of methotrexate.