Intestinal bacteria and endogenous production of malonaldehyde and alkylators in mice

Association of intestinal bacteria with endogenous production of some reactive compounds was studied by determination of adducts to haemoglobin in blood from germ-free and corresponding control mice. N-terminal valines in haemoglobin were analysed with regard to adducts from malonaldehyde (MA), ethene/ethylene oxide, propene/propylene oxide and methylating agents. It was found that the adduct levels from MA were 1.65 and 3.32 nmol/g globin in germ-free and control mice, respectively. The levels of adducts from ethylene oxide and propylene oxide were 10.8 and 10.3 pmol/g globin, respectively, in germ-free and 21.7 and 17.7 pmol/g globin, respectively, in control mice. The level of adducts from endogenous methylating agents was higher in germ-free mice than in controls (473 and 408 pmol/g globin, respectively). These differences in adduct levels between germ-free and conventional mice are statistically significant. The causes of the observed variations are so far not identified. This study confirms earlier findings on background levels of adducts in unexposed individuals and supports the hypothesis that these adducts reflect the occurrence of reactive intermediates in vivo that may constitute cancer risks in background cancer incidence. The present study also shows that intestinal bacteria may be an important determinant of such endogenous risk factors.