In general nitrosamines constitute a class of potent carcinogens that induce tumors in all rodent species, although the tumor sites do vary between species. There are only a few examples of non-carcinogenic nitrosamines that are not fully substituted at the alpha-positions and hence prevent alpha-hydroxylation (activation). Diallylnitrosamine (DAN) is one such compound and was reported non-carcinogenic in the BD rat. However, we have found DAN to be a potent inducer of respiratory tract tumors in the Syrian golden hamster upon multiple or a single subcutaneous (s.c.) injection. These comparative findings give rise to multiple questions concerning this type of species difference never observed before with nitrosamines. To determine some of the factors that may contribute to this dramatic species difference in light of the present knowledge about nitrosamine carcinogenesis the following studies are proposed: (1) determination of the carcinogenic response of the Syrian golden hamster and the BD(IX) rat to DAN using intragastric and subcutaneous administration; (2) determine if DAN is metabolically converted into other nitrosamines in either species using both i.g. and s.c. routes of administration; (3) determination of the qualitative and quantitative distribution of covalently bound adducts to nucleic acids in high and low risk tissues in the hamster and rat upon i.g. and s.c. administration of DAN-3H; (4) determination of the qualitative and quantitative persistence of specific alkylated components of nucleic acids in high and low risk tissues in both species, as determined from the proposed chronic animal testing.
NIH ExPorter
NIH ExPorter