Table 1.

A comprehensive list of studies using 4NQO as an oral carcinogen in mice, either by local (oral cavity brushing) or systemic (drinking water) delivery

YearAuthorsMouse backgroundDeliveryDoseCarcinogen administrationObservationLesions
1965Fujino et al. (13)ddNBrushing*2.5 mg/mLOnce a day until death25-80 wkOSCC
1984Steidler and Reade (28)CBABrushing5 mg/mLThrice a week, 2-16 wk50 wkPremalignant, OSCC
1986Steidler and Reade (29)CBABrushing5 mg/mLThrice a week, 2-16 wk50 wkPremalignant, OSCC
1994Hawkins et al. (18)CBABrushing5 mg/mLThrice a week, 4-16 wk49 wkPremalignant, OSCC
1994Yuan et al. (35)CBABrushing5 mg/mLThrice a week, 4-16 wk49 wkPremalignant, OSCC
1997Yuan et al. (36)CBA/JBrushing5 mg/mLThrice a week, 4-16 wk24 wkOSCC
1999Ma et al. (24)CBABrushing5 mg/mLThrice a week, 16 wk28 wkPremalignant, OSCC
1999Ma et al. (25)CBADW10 μg/mL16 wkUp to 44 wkDysplasia
1999von Pressentin et al. (33)CD-2; (BALB/c × DBA/2)F1 (MutaMouse)DW20-80 μg/mLMultiple schemes6 wkMutations
2000von Pressentin et al. (32)CD-2; (BALB/c × DBA/2)F1 (MutaMouse)DW20 μg/mL2 wk4 wkMutations, oral and aerodigestive tissues
2001Ishikawa et al. (21)CBA/C57BL/6 and CD-1 (XPA−/−, XPA+/−, XPA+/+)DW10 μg/mL50 wk50 wkPremalignant lesions, OSCC
2001Ide et al. (20)CBA/C57BL/6 and CD-1 (XPA−/−, XPA +/−, XPA +/+)DW10 μg/mL50 wk50 wkOSCC
2002Kim et al. (22)SENCARBrushing5 mg/mLThrice a week, 28 wk28 wkPremalignant lesions, OSCC
2002Guttenplan et al. (16)CD-2; (BALB/c × DBA/2)F1 (MutaMouse)DW20 μg/mL4 wk6 wkMutations
2003Ide et al. (19)C3H/HeN/C57BL/6/CBA (XPA−/− p53 +/−)DW10 μg/mL50 wk50 wkOSCC
2004Gannot et al. (14)BALB/cBrushing10 mg/mL16 wk24-32 wkOSCC
2004Tang et al. (31)CBABrushing5 mg/mLThrice a week, 16 wk8-16 wkOSCC, ESCC
2004Tang et al. (31)CBADW20, 50, 100 μg/mL16 wk8-16 wkOSCC, ESCC
2004Tang et al. (31)C57BL/6DW100 μg/mL16 wk8-16 wkOSCC, ESCC
2006Zhang et al. (37)FVB/J-BALB/c (p53Val135/WT)Brushing5 mg/mLThrice a week, 16 wk48 wkOSCC, ESCC, forestomach SCC
2006Fong et al. (12)C57BL/6J, p53−/−, +/−DW10-20 μg/mL21 wk21 wkOSCC, ESCC, forestomach SCC
2006Strati et al. (30)FVB/N (K14E6-E7)DW10 μg/mL16 wk24 wkPremalignant lesions, OSCC
2006Gunji et al. (15)ICR/129Sv (Parp-1−/+ and Parp-1−/−)DW10 μg/mL32 wk32 wkOSCC, ESCC, forestomach SCC
2008Miyamoto et al. (26)CB6F1-Tg-rasH2DW20 μg/mL2-8 wk24 wkPremalignant lesions, OSCC, ESCC
2008Young et al. (34)C57BL/6DW50 μg/mL16 wkUp to 32 wkPremalignant lesions, OSCC
2008Korpi et al. (23)C57BL/6 (MMP-8 KO)Brushing10 mg/mLThrice a week, 12 wk55 wkPremalignant lesions, OSCC
2008Dwivedi et al. (11)C57BL/6Brushing5 mg/mLDaily, 8 wkUp to 19 wkHyperplasia, dysplasia
2008Schoop et al. (27)CBABrushing5 mg/mLThrice a week, 16 wkUp to 40 wkOSCC
2009Czerninski et al. (10)C57BL/6DW50 μg/mL16 wk23 wkPremalignant lesions, OSCC
2009Hasina et al. (17)CBADW50, 100 μg/mL8 or 16 wkUp to 24 wkPremalignant lesions, OSCC

Abbreviations: OSCC, oral SCC; DW, drinking water; ESCC, esophageal SCC.

  • *Brushing: local administration of the carcinogen in the oral cavity. The indicated dose reflects the stock solution. Total dose may vary based on the delivery device used. Local delivery usually results in oral lesions exclusively.

  • The first laboratory to compare drinking-water with tongue-brushing administration of 4NQO in different strains of wild-type mice and to use oral SCC as an end point.

  • Complete autopsies, malignant proliferations restricted to oral cancer lesions.