TABLE 1

Metabolism of 3,5-dinitrobenzamide 2-mustard analogues (250 μM) by the S9 fraction of livers from various species in the presence of the cofactor NADPH

All values are mean ± S.D. peak area at 254 nm (mAU · s) of four replicate incubations. Total o- or p-nitroreduction denotes the sum of the corresponding hydroxylamine and amine metabolites.

SN 27858 (1)
o-Nitroreduction
p-Nitroreduction (1a + 1b)
N-Dealkylation
O-Acetylation (1j)
Human (HL5) ND 261 ± 9 ND 227 ± 107
Human (HL18) ND 3338 ± 1064 ND 369 ± 122
Mouse ND 3348 ± 1749 ND 99 ± 70
Rat (male) ND 705 ± 377 ND 54 ± 28
Rat (female) ND 1994 ± 818 ND 232 ± 93
Dog ND 589 ± 118 ND 153 ± 44
SN 29546 (2)
o-Nitroreduction
p-Nitroreduction (2a + 2b)
N-Dealkylation
O-Acetylation (2j)
Human (HL5) ND 934 ± 602 ND 504 ± 208
Human (HL18) ND 3501 ± 614 ND 454 ± 338
Mouse ND 2739 ± 1420 ND 472 ± 208
Rat (male) ND 3859 ± 984 ND 362 ± 86
Rat (female) ND 4040 ± 1127 ND 460 ± 271
Dog ND 113 ± 46 ND 484 ± 215
SN 27686 (3)
o-Nitroreduction (3d + 3e)
p-Nitroreduction (3b)
N-Dealkylation (3f + 3h)
O-Acetylation (2j)
Human (HL5) 892 ± 295 1888 ± 1056 3213 ± 1527 815 ± 248
Human (HL18) 1878 ± 436 3797 ± 740 3508 ± 3935 459 ± 146
Mouse 1131 ± 1027 1051 ± 1022 552 ± 213 40 ± 60
Rat (male) ND 396 ± 54 1308 ± 864 ND
Rat (female) ND 461 ± 345 166 ± 77 205 ± 168
Dog 874 ± 375 965 ± 513 908 ± 379 286 ± 27
SN 29893 (4)
o-Nitroreduction (4c)
p-Nitroreduction (4b)
N-Dealkylation (4f + 4g + 4i)
O-Acetylation (1j)
Human (HL5) 2441 ± 1011 1340 ± 283 8373 ± 989 1250 ± 496
Human (HL18) 2559 ± 661 1520 ± 287 7240 ± 858 662 ± 321
Mouse ND 2140 ± 323 6689 ± 1553 193 ± 11
Rat (male) 2085 ± 404 1698 ± 373 8189 ± 1414 323 ± 70
Rat (female) 1044 ± 423 945 ± 143 4924 ± 1412 198 ± 39
Dog
1303 ± 547
1796 ± 540
8572 ± 1124
182 ± 25

  • ND, not detected.