Hiroyuki Matsuoka

Parasite infection and cancer: with special emphasis on Schistosoma japonicum infections (Trematoda). A review

This article contains a review of current knowledge on the association of parasite infections and cancer formation, especially that of Schistosoma japonicum (Trematoda) in man and experimental animals. The association of S. haematobium infection and bladder cancer is well known and documented. However, S. japonicum infection has also been reported to be associated with cancer, in this case hepatocellular carcinoma and/or colorectal cancer. Pathological records and analyses have shown a correlation between this infection and cancer, and pathohistological descriptions have been numerous, together with clinical case reports. Epidemiological analyses have been conducted in China and Japan and support a role of S. japonicum infection as one of the risk factors in cancer formation, along with others, such as hepatitis virus infection and alcoholic intake. Experimental results have also shown that cancer appears early and in larger numbers in experimentally infected animals given a known carcinogen. In spite of these positive end-point associations, the mechanism of schistosome-mediated enhancement of carcinogenesis is obscure. A suggestive observation is that in S. japonicum-infected mice carcinogen-metabolizing hepatic activity including P-450 was decreased so that an administered carcinogen persisted for a longer period than in uninfected mice. Further studies, both epidemiological and experimental, are needed to firmly establish the relationship between schistosome infection and cancer.

ELISA inhibition method in detection of mite and chironomid antigens in environmental samples of dust, soil and air

To determine the amount of chironomids and mite antigens in the indoor and outdoor environment, we investigated samples from air, soil and house dust in the area around Lake Kojima, located in the western part of Japan. Three species of chironomid (Tokunagayusurika akamusi, Chironomus yoshimatsui and Chironomus plumosus) and a species of mite, Dermatophagoides farinae antigens were studied. The antigens were detected and quantified by inhibition ELISA. In the outdoor environment, C. yoshimatsui and T. akamusi antigens were more abundant than mite antigen, and seasonal fluctuations were observed. In the indoor environment, mite was the predominant antigen. D. farinae antigen was detected in almost all dust samples, with a slight reduction in winter compared to summer.

Evaluation of the mutagenicity and the tumor-promoting activity of parasite extracts: Schistosoma japonicum and Clonorchis sinensis.

In relation to the observed association of carcinogenesis with parasitic infections, the mutagenicity of extracts of Schistosoma japonicum and Clonorchis sinensis was examined. In the bacterial mutagenicity tests using the Ames Salmonella typhimurium strains TA98, TA100, TA97 and TA102, and Escherichia coli WP2 and WP2 uvrA pKM101 Schistosoma soluble egg antigen and a homogenate of adult Schistosoma worms showed no positive responses either in the presence or in the absence of S9 mix. Likewise, adult worm extracts of Clonorchis showed no mutagenicity. The Schistosoma soluble egg antigen showed a weak but significant activity for the induction of Epstein-Barr virus expression in viral genome-carrying human lymphoblastoid cells in culture. This phenomenon suggests that the soluble egg antigen possesses tumor-promoting activity.

Reduced levels of mutagen processing potential in the Schistosoma japonicum-infected mouse liver

Epidemiological studies have shown the presence of a positive correlation between the infection of Schistosoma japonicum and colorectal and/or liver cancers in the humans. To explore the mechanism underlying this correlation, we have investigated the mutagen-activating potentials of the liver homogenate fraction (S9) from Schistosoma japonicum infected mice and those from control mice, by use of the Ames test with 2-acetylaminofluorene, aflatoxin B1 and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) as test mutagens. Liver S9 prepared from the infected group at the 15th week after the infection showed a potential significantly lower than that from the control group. The hepatic cytochrome P-450 concentration in the infected mice was persistently low, about a half of that in the uninfected mice, during the period of 6-18 weeks after the infection. Thus, in mice bearing chronic schistosomiasis, mutagen-processing potentials are decreased.

Detection of IgE antibodies to larvae and adults of chironomids by enzyme‐linked immunosorbent assay

Using the ELISA method, IgE antibodies to chironomid midges; Tokunagayusurika akamusi larva (TAL), T. akamusi adult (TAA), Chironomus yoshimatsui larva (CYL), C. yoshimatsui adult (CYA) and Chironomus plumosus adult (CPA), were measured in the sera of 36 children with bronchial asthma who visited Tamano City Hospital near Lake Kojiima in the Okayama prefecture. IgE antibodies to adult midges (TAA, CYA and CPA) were widely detected, but only few IgE antibodies to larvae (TAL and CYL). The amount of IgE antibody to CYA and to CPA correlated (P < 0.001), but the amount of IgE antibody to TAA and to CYA or CPA did not. This suggests that the allergenicity of CYA and CPA is similar, but the allergenicity of TAA is independent of that of CYA or CPA. On the other hand, the ELISA inhibition test showed that TAA allergenicity was independent of that of TAL, CYL, CYA, CPA and the house‐dust mite, Dermatophagoides farinae (Df), The inhibition test also showed that CYA and CPA had similar allergenicity, but differed from TAL, TAA, CYL and Df. This indicates that the allergenicities of chironomid midges change during the metamorphosis from larva to adult, and are not common among all species.

Developmental change of chironomid allergen during metamorphosis.

The development of allergen during metamorphosis of chironomids, Chironomus yoshimatsui and Tokunagayusurika akamusi, was studied by means of ELISA inhibition with pooled serum containing high titer of specific IgE to each adult midge. Extracts of C. yoshimatsui larvae and pupae did not inhibit the specific IgE antibody to adult C. yoshimatsui. Mature adult C. yoshimatsui extract had about 10 times more inhibitory substance than the young adult. Hemoglobin, however, was degraded during the metamorphosis as measured by spectrophotometry and HPLC. The inhibitory substance against specific IgE antibody to adult T. akamusi was identified as highest in female body, less in egg, and even less in wing, leg and male body. The size of the substance in egg and female body was estimated at > 500 kD of molecular weight.

Modified metabolism of a carcinogen, 3-amino-1-methy-5H-pyrido[4,3-b]indole (Trp-P-2), by liver S9 from Schistosoma japonicum-infected mice

Schistosoma japonicum infection has been associated with an increased incidence of liver and colorectal cancers in humans. To explore the mechanisms underlying this association, we investigated the carcinogen-metabolizing properties of liver S9 preparations from S. japonicum-infected mice and compared them with those of S9 from uninfected animals. When the carcinogen 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) was incubated with these S9s and the products were analyzed by high-performance liquid chromatography, we observed that the S9 from infected mice had a lower ability to convert Trp-P-2 into 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2(NHOH)), an activated form of promutagenic Trp-P-2, than the S9 from uninfected mice. We found that both of these S9 preparations have a high ability to reduce Trp-P-2(NHOH) into Trp-P-2; however, the infected-mouse S9 showed a significantly greater reducing power than the control S9. This difference appears to be responsible for the observed lower mutagen-activating potential of the infected mouse S9. These results suggest that hepatic enzyme activities of S. japonicum-infected mice are quantitatively different from those of normal mice.