Effect of dietary aromatic isothiocyanates fed subsequent to the administration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone on lung tumorigenicity in mice.
Naturally-occurring aromatic isothiocyanates, benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC), were tested for their post-treatment effects on lung tumorigenicity by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice. Mice at 7 weeks of age were administered a single i.p. dose of NNK (10 mumol/mouse). One week after NNK dosing, mice were placed on AIN-76A diet containing 1 or 3 mumol/g diet of BITC or PEITC. The control group was maintained on AIN-76A diet after NNK administration. Mice were killed 16 weeks after NNK treatment and lung adenomas were counted. The results showed mice fed control diet developed 7.8 tumors/mouse. Mice fed PEITC at concentrations of 1 or 3 mumol/g diet had 8.2 or 6.1 tumors/mouse, respectively. Feeding BITC at 1 mumol/g diet resulted in a tumor yield of 8.0 tumors/mouse, whereas BITC diet at 3 mumol/g diet gave 5.2 tumors/mouse, a small but significant inhibition. However, in the high BITC dose group, a loss in weight gain due to reduced food intake was noted. The results of this study showed that post-treatment of aromatic isothiocyanates had little, if any, effect on NNK lung tumorigenicity in A/J mice. This is in contrast to our previous findings in which pretreatment with PEITC greatly inhibited lung tumor induction by NNK in A/J mice and suggests that tumor inhibition by PEITC is due to inhibition of NNK metabolic activation.
Morse
M A
MA
Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595.
Reinhardt
J C
JC
Amin
S G
SG
Hecht
S S
SS
Stoner
G D
GD
Chung
F L
FL
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D005260:Female; D017879:Isothiocyanates; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity*; D013861:Thiocyanates / Q000494:pharmacology*
D002273:Carcinogens; D017879:Isothiocyanates; D009602:Nitrosamines; D013861:Thiocyanates; C058305:phenethyl isothiocyanate; C051577:4-(methylnitrosoamino)-4-(3-pyridyl)-1-butanol; C031403:benzyl isothiocyanate