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Background: The aim of this study is to examine the inflammatory-cytokine expressions in the presence of noncytotoxic dose of methylmercury (MeHg) in murine macrophages, which is suspected to play an important role in brain damage caused by MeHg exposure. We focused on murine macrophage inflammatory protein-2 (MIP-2), keratinocyte chemoattractant (KC), and monocyte chemoattractant protein-5 (MCP-5). MIP-2 and KC are murine functional homologues of human IL-8 and MCP-5 for human MCP-1. Furthermore, we examined the suppressive effect of N-acetyl-l-cysteine (NAC) on the MeHg-induced inflammatory cytokines. Methods: In a murine RAW264.7 macrophage cell line, MeHg-induced cytokine expressions were measured using real-time PCR. The suppressive effect of NAC was examined by putting it into the culture medium together with MeHg (co-treatment). In addition, pre- and post-treatment experiments were conducted, in which the cells were treated with NAC before and after MeHg exposure, respectively. Results: Exposure to a non-cytotoxic dose of MeHg up-regulated the mRNA expression of MIP-2 and MCP-5. On the other hand, KC expression was not induced in the presence of MeHg. Effect of MeHg on MIP-2 expressions was suppressed by pre-, co-, and post-treatment with NAC. However, the suppressive effect of pre-treatment was less than the post-treatment, which was as effective as co-treatment. Conclusion: In functional homologues of human IL-8, only MIP-2 expression, not KC, was activated in the presence of non-cytotoxic dose of MeHg in murine RAW264.7 macrophage cell line. The more evident inhibitory effect of NAC observed in post-treatment experiments suggests a possible involvement of intracellular activities such as antioxidant effects. [ABSTRACT FROM AUTHOR]

Background: High birth weight (BW), 4000 g or larger, is an established risk factor for childhood leukemia. However, its association with central nervous system (CNS) tumor risk is yet unclear. The present study examined it, analyzing data obtained from a case-control study conducted among three states from the US. The association with childhood leukemia risk was also further examined.Methods: In this study, a data set provided by the Comprehensive Epidemiologic Data Resource was analyzed with an official permission. The original case-control study was conducted to examine the association between paternal preconception exposure to ionizing radiation and childhood cancer risk. Cases with childhood cancer were mainly ascertained from local hospitals, and controls were selected, matched with birth year (1-year category), county of residence, sex, ethnicity and maternal age (+/-2 years). Since the ID numbers were unavailable, conventional logistic analyses were conducted adjusting for those matching variables except for the county of residence. In addition to those variables, gestational age, age at diagnosis and study sites as covariables were included in the logistic models.Results: Analyzed subjects were 72 CNS tumor cases, 124 leukemia cases and 822 controls born from 1945 to 1989. The odds ratios (ORs) of CNS tumor risk for children with low BWs (<2500 g) and high BWs (>4000 g) were 2.0 (95% confidence interval [CI]) = 0.7, 5.9) and 2.5 (95%CI = 1.2, 5.2)], respectively. When high-BW children were restricted to those who were large for gestational age (LGA), the OR for high-BW children remained similar (OR = 2.7; 95%CI = 1.1, 6.2). On the other hand, the ORs of leukemia risk for children with low and high BWs were 0.8 (95%CI = 0.2, 3.0) and 1.4 (95%CI = 0.7, 2.6), respectively. In the normal range of BW (2500-4000 g), higher BW was positively associated with CNS tumor risk (beta = 0.0011, p for trend = 0.012). However, the association with leukemia risk was not significant (beta = -0.0002, p for trend = 0.475).Conclusion: High-BW and LGA children had an elevated childhood CNS tumor risk. In the normal BW range, the BW itself was positively related to CNS tumor risk. No significant association between BW and childhood leukemia risk was observed in this study. [ABSTRACT FROM AUTHOR]

Whether chronic exposure has an cancer risk per dose different from that of acute exposure is a topic of debate. This paper discusses the effect of dose rate on the strength of relationship between cancer risk and external exposure to low-LET (Linear Energy Transfer) ionizing radiation (such as X-rays and gamma rays), by reviewing important epidemiological studies. The study of atomicbomb survivors, who had acute exposure mainly to low- LET ionizing radiation, has shown that the excess relative risk per gray (ERR/Gy) of leukemia increases in a linearquadratic manner with an increase of radiation dose. The estimate of ERR/Gy for medium-high dose ranges was shown to be approximately two-fold larger than that for a low-dose range in the atomic-bomb survivor study. The estimate of ERR/Gy associated with acute exposure appears to be larger than those obtained from the studies of lowdose- rate exposure. On the other hand, the risk of solid cancer (or all cancers excluding leukemia) showed a linear dose-response relationship. Regarding the risk modification by dose rates, lower dose-rate exposure to high LET radiation is suspected to be associated with a larger risk. In the case of low-LET exposure, however, the cancer incidence study of residents in high natural background radiation areas of Karunagappally Taluk in Kerala State, India suggests that the ERR per dose for solid cancer after chronic radiation exposure is significantly lower than that associated with acute exposure such as that experienced by atomic-bomb survivors. [ABSTRACT FROM AUTHOR]