Hypochlorous acid (HOCl), a chemically reactive oxidant, is an important component of the inflammatory response and may contribute to carcinogenesis. This study assessed the possible activation of N-acetylbenzidine (ABZ) by HOCI to form a specific DNA adduct, N'-(3'-monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine. HOCl was incubated with 0.06 mM 3H-ABZ, and transformation assessed by HPLC. Similar results were observed at pH 5.5 or 7.4. A linear increase in transformation was observed from 0.025 to 0.1 mM HOCl with up to 80% of ABZ changed. Approximately, 2 nmoles of HOCI oxidized 1 nmole of ABZ. N-oxidation products of ABZ metabolism, such as N'-hydroxy-N-acetylbenzidine, were not detected. Oxidation of ABZ was prevented by taurine, DMPO, glutathione, and ascorbic acid, whereas mannitol was without effect. Results are consistent with a radical mechanism. In the presence of 2'-deoxyguanosine 3'-monophosphate (dGp), a new product (dGp-ABZ) was observed. The same adduct was observed with DNA. dGp-ABZ was found to be quite stable (>80% remaining) at 70 degrees C in pH 5.5 (60 min) and 7.4 (240 min). Electrospray mass spectrometry indicated that dGp-ABZ was N'-(3'-monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine, and this was confirmed by NMR. 32P-postlabeling in combination with TLC and HPLC determined that the adduct made by either HOCl or prostaglandin H synthase oxidation of ABZ in the presence of dGp or DNA was dGp-ABZ. Thus, HOCI activates ABZ to form dGp-ABZ and may be responsible for the presence of this adduct in peripheral white blood cells from workers exposed to benzidine. Reaction of ABZ with HOCl provides an easy, convenient method for preparing dGp-ABZ.

Abstract. Most patients with rectal cancer are treated with curative-intent surgery; adjuvant chemotherapy and radiation are often used as well. A recent survey of members of the American Society of Colon and Rectal Surgeons (ASCRS) revealed considerable variation in surveillance intensity after primary treatment. We evaluated whether geographic factors may be responsible for the observed variation. Vignettes of hypothetical patients and a questionnaire based on the vignettes were mailed to the 1782 members of ASCRS. Repeated-measures analysis of variance was used to compare practice patterns, as revealed by the responses, according to US Census Regions and Divisions, Metropolitan Statistical Areas (MSA), and state-specific managed care organization (MCO) penetration rates. There was significant variation in surveillance intensity according to the US Census Region and Division in which the surgeon practiced. Non-US respondents employed CT of the abdomen and pelvis, chest radiography, and colonoscopy significantly more often than US respondents. MSA was not a significant source of variation. Surveillance patterns varied significantly by MCO penetration rate for office visits and CT of the abdomen and pelvis but not for other modalities. The US Census Region and Division in which the surgeon practices have a significant effect on surveillance intensity following completion of primary curative-intent therapy for rectal cancer patients. The MSA in which the surgeon practices does not affect surveillance intensity significantly and MCO penetration rate affects follow-up intensity minimally. All significant differences are clinically rather modest, however. These data should be useful in the design of controlled trials on this topic.

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