Inhibitory effects of 2-n-heptylfuran and 2-n-butylthiophene on benzo[a]pyrene-induced lung and forestomach tumorigenesis in A/J mice.
Many furan-containing natural products that induce increased activity of the glutathione S-transferase (GST) enzyme system have been found to inhibit tumorigenesis in laboratory animals. 2-n-Heptylfuran (HF) and 2-n-butylthiophene (BT), a sulfur analogue of furan, are two of the many furans and thiophenes formed during the roasting process of meat. BT and HF, when administered by gavage at doses that ranged from 11 to 90 mumol, induced increased GST activity in various tissues of A/J mice. At 90 mumol/dose, BT induced increased GST in the liver, small bowel mucosa, and lung. No increase in enzyme activity was found in the forestomach. HF was an enzyme inducer in the liver, small bowel mucosa, and forestomach but was inactive in the lung. The acid-soluble sulfhydryl level, a good measure of glutathione contents in tissues, was examined in tissue homogenates from mice treated with BT and HF. BT induced significant increase of GSH in the liver and lung at the higher doses. No change was observed in either the small bowel mucosa or the forestomach. A 50-mumol dose of HF was found to increase GSH level in all four tissues studied. The inhibition of lung and forestomach tumorigenesis was carried out with A/J mice using benzo[a]pyrene as the carcinogen. BT treatment resulted in a reduction of tumor multiplicity in the lung and forestomach. The tumor incidence in the forestomach was reduced significantly. The potency of HF as inhibitor of carcinogenesis was similar to that of BT in the forestomach of mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Lam
L K
LK
Gray Freshwater Biological Institute, University of Minnesota, Navarre 55392.
Zheng
B L
BL
D000818:Animals; D001564:Benzo(a)pyrene; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005663:Furans / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis; D005982:Glutathione Transferase / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013876:Thiophenes / Q000494:pharmacology*
D005663:Furans; D013876:Thiophenes; C072020:2-n-butylthiophene; D001564:Benzo(a)pyrene; D005982:Glutathione Transferase; D005978:Glutathione