Differential development of aldehyde dehydrogenase in fore- and glandular stomach in postnatal rats

Many foods contain the unsaturated aldehyde, hexadienal (HX). Human exposure is thus unavoidable. HX feeding to rodents caused cancers only in the forestomach. Aldehyde dehydrogenases (ALDH) are key enzymes in the metabolism of aldehydes. We examined the distribution of ALDH using HX as the substrate (HXDH) along the GI tract of adolescent rats and found that their stomachs have high levels of HXDH activity and the enzyme preferred HX > 9-cis-retinal > acetyl aldehyde > formyl aldehyde. We also followed the postnatal development of the stomach. At birth, the forestomach represented 40-50% of the total stomach weight. Both fore- and glandular stomach gained weight, with the glandular portion gaining at a faster rate. By 21 days, the forestomach was 24-28% of the total weight and decreased slightly to an adult level of 22-24%. Gastric HXDH is low from birth to 14 days of age. HXDH activity increased thereafter, reaching higher levels at 21 days and peaking around 30-36 days of age. The activity then decreased to the adult level. The fore- and glandular stomach had the same level of HXDH activity in the newborn and at 7 and 14 days of age. At weaning, HXDH activity was higher (3x) in the forestomach than in the glandular stomach. In adults, the forestomach still had 2x the HXDH activity compared to the glandular stomach. Zymograms showed similar isozyme patterns of HXDH but with different ratios of the three major forms between the forestomach and the glandular stomach. Results indicate a differential development of HXDH between the fore- and glandular stomach that might be related to the higher sensitivity of the forestomach to HX feeding.