Carcinogenesis Insecticides

Fransson-Steen R, Rodstrom S, Warngard L. 1992. The insecticide endosulfan and its two stereoisomers promote the growth of altered hepatic foci in rats. Carcinogenesis 13(12) 2299-2303. 

Lijinsky, W. and D. Schmal. 1978. Carcinogenesis by nitroso derivatives of methylcarbamate insecticides and other nitrosoamides in rats and mice. Pages 495-501 in E.A. Walker, M. Castenegro, L. Griciute, and R.E. Lyle (eds.). Environmental Aspects of N-nitroso Compounds. World Health Qrg., Int. Agency Res. Cancer, IARC Sci. Publ. 19. 

Carcinogenesis in mice 2 year diet, at 400 ppm appears liver tumors 120-130 0.562 Insecticide... 

Epoxidation Epoxidation is an important microsomal reaction. For example, the cyclodiene insecticide aldrin can be oxidized to its epoxide dieldrin (as shown in Chapter 4, Figure 4.4), and heptachlor is oxidized to heptachlor epoxide. There is no great increase in toxicity in this case, but the epoxides are more environmentally persistent than their precursors. Moreover, some of the epoxides produced in the microsomal oxidation are highly reactive and can form adducts with cellular macromolecules such as proteins, RNA, and DNA, often resulting in chemical carcinogenesis. 

Hermann KG (1987) FCR 1272 (c.n. cyfluthrin) Study for acute oral toxicity to rats (formulation acetone and peanut oil). Bayer Corporation Agricultural Division Report No. 106805. Hemming H, Flodstrom S, Wamgard L (1993) Enhancement of altered hepatic foci in rat-liver and inhibition of intercellular communication in-vitro by the pyrethroid insecticides fenvalerate, flucythrinate and cypermethrin. Carcinogenesis 14 2531-2535 Henrick CA (1977) Zoecon Corp. (patent for fluvalinate development). 

Second, the use of S-9 assumes that no mitochondrial or nuclear enzymes could have a direct involvement in mutagenesis. It is only speculative at this point not to agree necessarily with this assumption. However, there is evidence that an isomer of the insecticide DDD used in the treatment of adrenal cortical carcinoma, Mitotane, is converted to covalently binding species by mitochondria, but not by microsomes or the soluble fraction isolated from canine adrenal cortex tissue. Likewise, Bresnick has postulated that the nuclear mixed-function oxidases contribute in vivo to that activation of polycyclics that leads to mutagenesis and carcinogenesis, while the enzymes in the endoplasmic reticulum (microsomes) are more involved with the detoxification of these chemicals. Bresnick et have demonstrated with histofluorescence tech-... 

---