TABLE E2. MUTAGENICITY OF NITROFURANTOIN IN MOUSE L5178Y LYMPHOMA CELLS (a.b) 



Cloning Relative Mutant Mutant 



Compound Concentration Efficiency Total Growth Count Fraction (c) 



(Hg/ml) (percent) (percent) 



Trial 1 



Dimethyl sulfoxide (d) 108.0 ± 00 100.0 116.0 114.5 ± 4.5 35.5 ± 1.5 



Nitrofurantoin 50 90.0 ± 46 65.0 ± 3.2 145.0 ± 5.6 53.7 ± 1.8 



100 81.3 ± 5.9 44.7 ± 3.5 245.3+ 19.6 (e) 101.0 ± 3.6 



150 79.3 ± 11.5 26.7+ 1.2 472.7+ 97.1 (e)196.3± 13.7 



200 70.5 ± 4.5 22.5 ± 3.5 417.0 ± 181.0 (e) 194.0 ± 74.0 



(f)300 67.3 ± 5.2 15.0 ± 1,5 586.7+ 44.6 (e)292.0± 12.1 



500 54.3 1 3.9 9.0 1 0,6 485.7 1 41.2 (e)297.7+ 13,9 



Methyl methanesulfonate 5 80.3 1 5.2 56.3 1 2.3 684.0 1 29.0 (e)285.3+ 6.1 



Trial 2 



Dimethyl sulfoxide (g) 84.0 1 17 100.0 1 6.1 63.5 1 8.1 25.3+ 3.0 



Nitrofurantoin 50 84.7+ 5.6 65.0 1 2,6 102.7+ 26.5 (e)40.0+ 8.7 



100 75.0+ 1,2 42,3+ 3,5 137.3 1 33.2 (e)60.7i 14.2 



150 61.0 1 26 27.7 1 0.9 142.3 1 26.7 (el78.3 1 14.7 



200 59.7 110,7 15.0 1 2.0 245.3 1 40.6 (e) 144.0 1 31.9 



lf)300 37.3 1 5.6 6.3 1 1.2 297.0 1 38.2 (e)270.7 1 29.2 



500 19.3 1 2.8 2.0 1 0.0 189.3 1 61.1 (ei374.0 1 141.5 



Methyl methanesulfonate 5 56,7 1 6.1 44.0+ 3,5 247.7 1 20.2 (ei 149.0 1 20.0 



(a I Study performed at Litton Bionetics, Inc. The experimental protocol is presented in detail by Myhr et al. (1985) and follows 

 the basic format of Clive et al. (1979). The highest dose of study compound is determined by solubility or toxicity and may not 

 exceed 5 mg/ml. All doses are tested in triplicate; the average for the three tests is presented in the table. Cells (6 X lOWml) 

 were treated for 4 hours at 37° C in medium, washed, resuspended in medium, and incubated for 48 hours at 37° C. After ex- 

 pression, 3 X 106 cells were plated in medium and soft agar supplemented with trifluorothymidine for selection of cells that 

 were mutant at the thymidine kinase (TK) locus, and 600 cells were plated in nonselective medium and soft agar to determine 

 the cloning efficiency. All trials were conducted in the absence of S9. 



(b)Mean 1 standard error from replicate trials of approximately 1 x lO^cellseach, unlessotherwise noted. All data are evalu- 

 ated statistically for both trend and peak response ( P< 0.05 for at least one of the three highest dose sets). Both responses must 

 be significantly (P<0.05) positive for a chemical to be considered mutagenic. If only one of these responses is significant, the 

 call is "equivocal"; the absence of both trend and peak response results in a "negative" call. 



(c) Mutant fraction (frequency) is a ratio of the mutant count to the cloning efficiency, divided by 3 (to arrive at MF per 1 X 10^ 

 cells treated); MF = mutant fraction. 



(d) Data presented are the average of two tests. 



le) Significant positive response; occurs when the relative mutant fraction (average MF of treated culture/average MF of sol- 

 ventcontrol) isgreater than or equal to 1.6. 



(f) Precipitate formed at this and all higher concentrations. 



(g) Data presented are the average of four tests 



195 Nitrofurantoin, NTFTR 341 



