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The implications of delta-aminolevulinic acid dehydratase (ALAD) polymorphism for lead kinetics and toxicity have been mainly studied in occupationally exposed adults. Therefore, our purpose was to evaluate the distribution of ALAD genotype and its association with biomarkers of exposure (PbB levels) and effect (Blood ZPP) among children living in a smelter community in Mexico. We recruited 569 children from nine elementary schools close to a smelter site. PbB was determined by electrothermal atomic absorption spectrometry. A polymerase chain reaction (PCR)-based protocol was used for ALAD genotyping. Zinc protoporphyrin (ZPP) in blood was measured by direct fluorometry. Most children (93.15%) were homozygous for ALAD (1-1), 6.67% were heterozygous for ALAD for (1-2), and one child was homozygous for ALAD (2-2). There was an increased proportion of ALAD (1-2/2-2) genotype with respect to PbB levels. The ZPP geometric mean was slightly higher in ALAD (1-1) genotype children (63.48 mu mol ZPP/mol Hb) than in those having the ALAD-2 genotype (58.22 mu mol ZPP/mol Hb; p = 0.051). Linear and quadratic models showed significant relationships between ZPP and PbB. A significant increase in the odds ratio (OR) for the effect of lead exposure on ZPP levels was observed for ALAD (1-1) children having PbB values above 20 mu g/dL, as compared to those having PbB levels below 10 mu g/dL (OR = 2.95, 95% CI = 1.45-5.97; p = 0.003), whereas no significant increases were observed for the ALAD (1-2/2-2) children. In summary, our results suggest that heme biosynthesis was less affected in ALAD (1-2/2-2) lead-exposed children than in those carrying the ALAD (1-1) genotype.

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We report the chemical composition of PM10-associated water-soluble species in Mexico City during the second semester of 2000. PM10 samples were collected at four ambient air quality monitoring sites in Mexico City. We determined soluble ions (chloride, nitrate, sulfate, ammonium, sodium, potassium), ionizable transition metals (Zn, Fe, Ti, Pb, Mn, V, Ni, Cr, Cu) and soluble protein. The higher PM(10) levels were observed in Xalostoc (45-174 microg m(-3)) and the lowest in Pedregal (19-54 microg m(-3)). The highest SO2 average concentrations were observed in Tlalnepantla, NO2 in Merced and O3 and NO(x) in Pedregal. The concentration range of soluble sulfate was 6.7-7.9 and 19-25.5 microg m(-3) for ammonium, and 14.8-29.19 for soluble V and 3.2-7.7 ng m(-3) for Ni, suggesting a higher contribution of combustion sources. PM-associated soluble protein levels varied between 0.038 and 0.169 mg m(-3), representing a readily inhalable constituent that could contribute to adverse outcomes. The higher levels for most parameters studied were observed during the cold dry season, particularly in December. A richer content of soluble metals was observed when they were expressed by mass/mass units rather than by air volume units. Significant correlations between Ni-V, Ni-SO4(-2), V-SO4(-2), V-SO2, Ni-SO2 suggest the same type of emission source. The variable soluble metal and ion concentrations were strongly influenced by the seasonal meteoclimatic conditions and the differential contribution of emission sources. Our data support the idea that PM10 mass concentration by itself does not provide a clear understanding of a local PM air pollution problem.

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Our objective was to evaluate alterations in sperm chromatin structure in men occupationally exposed to a mixture of organophosphorus pesticides (OP) because these alterations have been proposed to compromise male fertility and offspring development. Chromatin susceptibility to in situ acid-induced denaturation structure was assessed by the sperm chromatin structure assay (SCSA). Urinary levels of alkylphosphates (DAP) were used to assess exposure. Diethylthiophosphate (DETP) was the most frequent OP metabolite found in urine samples indicating that compounds derived from thiophosphoric acid were mainly used. Chromatin structure was altered in most samples. About 75% of semen samples were classified as having poor fertility potential (>30% of Percentage of DNA Fragmentation Index [DFI%]), whereas individuals without OP occupational exposure showed average DFI% values of 9.9%. Most parameters of conventional semen analysis were within normality except for the presence of immature cells (IGC) in which 82% of the samples were above reference values. There were significant direct associations between urinary DETP concentrations and mean DFI and SD-DFI but marginally (P = 0.079) with DFI%, after adjustment for potential confounders, including IGC. This suggests that OP exposure alters sperm chromatin condensation, which could be reflected in an increased number of cells with greater susceptibility to DNA denaturation. This study showed that human sperm chromatin is a sensitive target to OP exposure and may contribute to adverse reproductive outcomes. Further studies on the relevance of protein phosphorylation as a possible mechanism by which OP alter sperm chromatin are required.

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The aim of this paper is to estimate the levels of arsenic (As) ingestion through cooked foods consumed in an arsenic endemic area and the assessment of their dietary intake of As. The study was conducted in two villages: a population chronically exposed to a high concentration of As via drinking water (410+/-35 microg/l) and to a low-exposure group (12+/-4 microg/l). A 24-h dietary recall questionnaire was applied to about 25 adult participants in each community. Samples of cooked food, ready for intake, were collected separately from each family's participants. To obtain the As estimate for each food item consumed, the mean quantity of food ingested in grams (wet weight) was calculated and the concentrations of total arsenic (TAs) in each cooked food were determined. The estimations of TAs intake were based on the sum over mean of As ingested from each food item consumed during the 24-h period for each participant. For the estimation of total daily As intake, we summed the mean obtained from food, plain water and hot beverage intakes. The TAs average intakes calculated for low-As-exposure group were 0.94 and 0.76 microg/kg body weight/day, for both summer and winter exposure scenarios, respectively. These values are 44.7 and 36% of the provisional tolerable daily intake (PTDI) for inorganic arsenic (2.14 microg/kg body weight/day), established by the World Health Organization (WHO) in 1989. The WHO reference value was obtained on a weekly basis intake estimation assuming an average body weight of 68 kg in adults. In contrast, for the high-exposure group the TAs average intakes were 16.6 and 12.3 microg/kg body weight/day for summer and winter, respectively. Ingestion via cooked food represented 32.5 and 43.9% of the total daily As intake in the high-exposure group; for summer and winter, respectively. None the less, the bioavailability of As through food can be different than via drinking water.

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Information on the association between exposure to beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB) or polychlorinated biphenyls (PCBs) and the incidence of breast cancer is inconclusive. However, exposure to such compounds is a public health concern in Mexico and is subject to recent regulation. Serum levels of beta-HCH, HCB and PCBs were analysed in 95 histologically confirmed breast cancer cases and 95 hospital controls, 20-79 years of age, from Mexico City, enrolled between March 1994 and April 1996. After adjusting for established risk factors, there was no evidence of a relationship between beta-HCH, HCB and PCBs and breast cancer risk (OR for beta-HCH tertile 3 versus tertile 1: 1.05 95% CI 0.46-2.40; OR for HCB tertile 3 versus tertile 1: 0.46 95% CI 0.20-1.07; OR for PCBs 1.31 95% CI 0.33-5.21 for the high category of exposure). This study lends no support to the case for a role for beta-HCH, HCB or PCBs in breast cancer aetiology.

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The role of cytochrome P450 (CYP) and the CYP isoform involved in the activation of the widely used pesticide methyl-parathion (MePA) were investigated in rat brain extracts by measuring the effect of different CYP inhibitors on acetylcholinesterase (AChE) inhibition by MePA. Brain extracts provide a useful tool to study the activation mechanisms of organophosphorus compounds (OP) since they contain both the activating enzyme(s) and the molecular target for OP toxicity. As expected, in incubations of rat brain extract supplemented with NADPH, AChE activity was non-competitively inhibited by the presence of MePA, indicating that MePA was activated to its reactive metabolite methyl-paraoxon (MePO). Indeed, Vmax(app) decreased from 13.4 to 8.7 micromol thionitrobenzoic acid (TNB)/min per mg protein. MePA activation by rat brain extracts, as measured by the AChE inhibition produced by the presence of the pesticide in the incubation, was fully prevented by previously bubbling the incubation mix with CO, by the presence of monoclonal anti-rat CYP2B1/2B2 antibodies and by the addition of phenobarbital (PB), a CYP2B substrate. Interestingly, MePA showed a greater affinity for CYP2B than PB. CYP1A1 antibodies showed no effect on MePA activation. The presence of cytochrome P450 2B (CYP2B) in the rat brain extracts was confirmed by immunoblotting. These results demonstrate indisputably the responsibility of CYP2B in MePA activation in the rat brain in vitro, suggesting that metabolic activation of OP compounds in situ might be crucial for their organ specific toxicity to the central nervous system also in vivo.

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Industrial growth has created the potential for environmental problems in Mexico, since attention to environmental controls and urban planning has lagged behind the pace of industrialization. The aim of this cross-sectional study was to assess lead exposure in children aged 6-9 yr attending 3 primary schools and living in the vicinity of the largest smelter complex in Mexico. One of the schools is located 650 m distant from a smelter complex that includes a lead smelter (close school); the second is located 1750 m away from the complex and at the side of a heavy traffic road (intermediate school) in Torreon, Coahuila. The third school is located in Comez Palacio, Durango, 8100 m away from the smelter complex and distant from heavy vehicular traffic or industrial areas (remote school). Lead was measured in air, soil, dust, and well water. Lead in blood (PbB) was determined in 394 children attending the above mentioned schools. Determinations were performed by atomic absorption spectrometry. Diet, socioeconomic status, hygienic habits, and other variables were assessed by questionnaire. Median (range) PbB values were 7.8 microg/dl (3.54-29.61) in the remote school, 21.8 microg/dl (8.37-52.08) in the intermediate school and 27.6 microg/dl (7.37-58.53) in children attending the close school. The percentage of children with PbB > 15 microg/dl was 6.80%, 84.9%, and 92.1% respectively. In this order, the geometric means (range) of Pb concentrations in air were 2.5 microg/m3 (1.1-7.5), 5.8 microg/m3 (4.3-8.5), and 6.1 microg/m3 (1.6-14.9). The Pb concentrations in dust from playgrounds areas in the intermediate and close school settings ranged from 1,457 to 4,162.5 mg/kg. Pb concentrations in drinking water were less than 5 microg/L. Soil and dust ingestion and inhalation appear to be the main routes of exposure. Our results indicate that environmental contamination has resulted in an increased body burden of Pb, suggesting that children living in the vicinity of the smelter complex are at high risk for adverse effects of lead.

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Dichlorodiphenyltrichloroethane (DDT) is a well-known inducer of microsomal monooxygenase systems in rodent liver. However, little information is available on its effects on the sex-dependent regulation of CYPs preferentially affected. Therefore, our objective was to evaluate the effects of DDT on the sexual expression pattern of some hepatic P-450 isozymes. Single doses of technical DDT (0, 0.1, 1, 5, 10, or 100 mg/kg body wt) were administered by gavage to Wistar rats. The effects on CYPs 1A1, 2B11/2B2, 2C11, 2E1, 3A1, and 3A2, were assessed 24 h later by means of CYP protein content determined by Western blotting and/or enzyme activities participating in alkoxyresorufin and pnitrophenol metabolism. The highest dose induced 18-fold the expression of CYP3A2 in female rats without producing significant induction (< 3-fold) in males. The effects on this isozyme, which is not normally expressed in females, suggest that DDT is able to modulate sexual metabolic dimorphism, as 3A2 expression is androgen dependent. DDT did not significantly alter CYP3A1 in males, suggesting that DDT is not a pure phenobarbital (PB)-type inducer. The effects on CYP2B1/2B2 protein (19-fold) and associated enzyme activities indicated that males had a lower response threshold than females, but that the latter were able to reach a higher relative induction. The preferential induction of CYPs 2B and 3A by DDT in a sex-related manner suggest that CYP regulation could play an important role in endocrine disruption.

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The ability of chromium (Cr) salts to increase metallothionein (MT) levels in rat liver, kidney and pancreas, and its relationship with the presence of toxic effects are reported here. Rats were injected subcutaneously with 0, 10, 20, 30, 40, or 50 mg K2Cr2O7/kg and sacrificed 24 h later. Total Cr accumulation followed a dose-dependent pattern, levels in kidney being higher than those in liver or pancreas, suggesting different tissue bioavailabilities and accumulation patterns. Cr(IV) administration resulted in a tissue-specific MT induction: pancreas and liver showed five- and 3.5-fold MT increases, respectively; no increase was observed in the kidney. A positive correlation was observed between zinc and MT concentrations in liver, and between total Cr and MT concentrations in pancreas. Serum alpha-amylase activity showed a dose-dependent increase starting from 20 mg/kg, whereas serum glucose levels increased at doses higher than 30 mg/kg. Serum aspartate aminotransferase and alanine aminotransferase activities were increased in a dose-dependent manner, from 20 and 30 mg/kg, respectively. Our results showed that treatment with Cr(VI) can induce MT synthesis in pancreas and suggests a subsequent binding of Cr to MT. Also, pancreas is a target organ for Cr toxicity, and the usefulness of alpha-amylase activity as a sensitive biomarker of Cr toxicity in human exposed populations merits further study.

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