Effect of Arterial Infusion of Bleomycin on Esophageal Carcinoma -- An Evaluation by Nuclear Cytophotometry --

In order to determine the histological changes after a singleinfusion of bleomycin (BLM) into the aortic esophageal artery(BLM A.I.), resected specimens from 58 patients with esophagealcarcinoma (27 cases with BLM A.I., 14 untreated cases, 13 caseswith radiation therapy and four cases with combined therapyof radiation and BLM) were examined and evaluated by Feulgenmicrospectrometry for nuclear deoxyribonucleic acid (DNA) content.The histological changes following the BLM A.I. were characterizedby degeneration and necrosis at the front of the invading carcinomatissue accompanied by inflammatory cell infiltration with foreignbody giant cells and fibrosis. In comparison with untreatedcases, BLM-treated cases showed an increase in nuclear DNA contentand a wide dispersion of the DNA values especially at the perinecroticarea and at the front of advancing carcinoma nests. Therefore,a histological effect of the BLM A.I. was shown by the measurementof the nuclear DNA content of carcinoma cells.     

Changes in the enzymatic activities of beagle liver during maturation as assessed both in vitro and in vivo

1. The metabolism of 50 μM [3-¹⁴C] coumarin has been studied in a panel of 12 human liver microsomal samples of known P450 isoenzyme profile.

2. [3-¹⁴C] coumarin was metabolized by human liver microsomes to various polar products including 3-, 4- and 7-hydroxycoumarins (3-HC, 4-HC and 7-HC) 6,7-dihydroxycoumarin (6,7-DiHC), o-coumaric acid (o-CA), o-hydroxyphenyl-acetaldehyde (o-HPA), o-hydroxyphenylethanol (o-HPE), o-hydroxyphenylacetic acid (o-HPAA) and o-hydroxyphenylpropionic acid (o-HPPA) and to product(s) that bind covalently to microsomal proteins.

3. For all 12 subjects, mean rates of [3-¹⁴C] coumarin metabolism to total polar products (metabolism to all products except product(s) covalently bound to microsomal proteins), 7-HC, the 3-hydroxylation pathway (sum of 3-HC, o-HPA, o-HPE and o-HPAA), o-HPPA, 6,7-DiHC and covalent binding were 1420, 1230, 73.8, 52.5, 9.5 and 4.8 pmol/min/mg protein respectively.

4. Marked interindividual differences in [3-¹⁴C] coumarin metabolism to total polar products (30-fold variation) and 7-HC (2250-fold variation) were observed.

5. Good correlations were observed between [3-¹⁴C] coumarin metabolism and total polar products, 7-HC, o-HPPA and 6,7-DiHC, but not to 3-hydroxylation pathway products and levels of 2A6 and 2B6 in human liver microsomes.

6. [3-¹⁴C] coumarin metabolism to any polar products did not correlate with levels of 1A2, 2C8, 2C9, 2E1, 3A3/4 and 4A1 in human liver microsomes.