2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) is the most abundant heterocyclic amine formed in meat and fish during cooking and can be used as a model compound for this class of chemicals possibly involved in human carcinogenesis. Knowing the exposure to heterocyclic amines is important for establishing their role in human diseases. Serum albumin (SA) and globin (Gb) adducts were first tested as biomarkers of exposure to PhIP in male Fischer 344 rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected 24 hr after treatment and PhIP released from SA and Gb after acidic hydrolysis was analyzed by gas chromatography‐mass spectrometry or liquid chromatography‐tandem mass spectrometry. PhIP‐SA and Gb adducts increased linearly with the dose. Studies on 35 volunteers with different dietary habits exhibited that diet was a major determinant in the formation of both adducts. PhIP‐SA adducts were significantly higher in meat consumers than in vegetarians (6.7 ± 1.6 and 0.7 ± 0.3 fmol/mg SA; respectively, mean ± SE; p = 0.04, Mann‐Whitney U test). The Gb adduct pattern was quantitatively lower but paralleled SA (3 ± 0.8 in meat consumers and 0.3 ± 0.1 in vegetarians). PhIP‐SA adducts were no different in smokers and in non‐smokers. The results show for the first time that PhIP‐blood protein adducts are present in humans not given the synthetic compound. Both biomarkers appear to be suitable for assessing dietary exposure and internal PhIP dose and may be promising tools for studying the role of heterocyclic amines in the etiology of colon cancer and other diseases. Int. J. Cancer 88:1–6, 2000. © 2000 Wiley‐Liss, Inc.

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The effect of organophosphate pesticide chlorpyrifos (CPF) on acetylcholinesterase (AChE) activity and on skeletal muscle development in Xenopus laevis larvae was studied. To achieve our purpose embryos were exposed to 100, 250 and 3000 microg/l CPF concentrations from late blastula stage (8 h postfertilization, p.f.) to stage 47 (120 h p.f.) and the appearance of AChE activity was monitored every 24 h. Compared with control, CPF treated larvae showed a dose dependent AChE inhibition during the early stages (beginning from 24 h until 120 h p.f.) that are crucial for neuromuscular development. The amount of AChE activity that can still be measured in treated larvae at stage 47 relative to that of the control, ranged from 28% in CPFs 100 microg/l to 4% in CPFs 3000 microg/l. These low AChE activities were associated with muscular damages such as reduced myotome size and hypertrophies coupled with extensive vacuolated regions in myocytes. The occurrence of this tissue-specific injury was related to CPF concentrations and was most pronounced in CPFs 3000 microg/l which revealed a very severe AChE inhibition during the exposure. Since AChE is the major neurotransmitter of the neuromuscular system, this initial descriptive study will be an useful starting-point to ongoing and future subcellular/molecular studies that correlate the morphological damage with changes in AChE activity.

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The study has explored two conservative biomarkers, porphyrin pattern in guano and methemoglobin levels in blood of Columba livia, in order to assay their potential use for monitoring toxic effects induced by exposure to urban air pollution. Fieldwork was conducted between October 2003 and June 2005 in the city of Milan, Italy, by sampling the pigeons in different areas almost twice a week. Six air contaminants, CO, PM10, NO(2), O(3), SO(2), and C(6)H(6), plus polycyclic aromatic hydrocarbons (PAHs) in fine particles, temperature, and UV index, were considered. Protoporphyrins from pigeon excreta sampled outdoors were always higher than in indoor animals, particularly in winter. A positive correlation (p < 0.001) of protoporphyrin with PAHs was observed. In terms of the values of methemoglobinemia, animals exposed to urban air showed significant differences from season to season but only in summer and autumn did the outdoor pigeons show higher values than indoor animals. In summer, a regression model with a positive correlation between O(3) and benzene was determined (p < 0.01). The use of Columba livia as a sentinel for urban air pollution as well as for detecting complex interactions between contaminants in the urban air pollutant mixture was discussed.