Herbicide enhanced metabolism

The mixed-function oxidase inhibitors aminobenzotriazole and piperonyl butoxide can synergize herbicide activity in resistant Lolium growing in a hydroponic system. This indicates that at least one aspect of cross-resistance in Lolium rigidum may be related to enhanced metabolic activity of mixed-function oxidazes acting to detoxify herbicides. We are now concentrating on direct studies of herbicide metabolism in resistant biotypes. 

Nontarget-site resistance is caused by mechanisms that reduce the amount of herbicidally active compound reaching the target site. An important mechanism is enhanced metabolic detoxification of the herbicide in the weed, with the effect that only insufficient amounts of herbicidally active substance will reach the target site. Furthermore, reduced uptake and translocation or sequestration of the herbicide may lead to insufficient herbicide transport to the target site. 

Cross-resistance means that a single resistance mechanism causes resistance to several herbicides. The term target-site cross-resistance is used when these herbicides bind to the same target site, whereas nontarget-site cross-resistance is due to a single nontarget-site mechanism (e.g., enhanced metabolic detoxification) that entails resistance across herbicides with different modes of action. 

Enhanced metabolism resistance (EMR). This is the most conunon mechanism and develops slowly over mar years. Herbicides affected by enhanced metabolism are broken down (detoxified) mote rapidly in resistant than susceptible plants. Each time the same herbicide is sprayed more of the resistant plants will remain so that gradually the weed population will be dominated by the more resistant plants. 

Compounds that affect activities of hepatic microsomal enzymes can antagonize the effects of methyl parathion, presumably by decreasing metabolism of methyl parathion to methyl paraoxon or enhancing degradation to relatively nontoxic metabolites. For example, pretreatment with phenobarbital protected rats from methyl parathion s cholinergic effects (Murphy 1980) and reduced inhibition of acetylcholinesterase activity in the rat brain (Tvede et al. 1989). Phenobarbital pretreatment prevented lethality from methyl parathion in mice compared to saline-pretreated controls (Sultatos 1987). Pretreatment of rats with two other pesticides, chlordecone or mirex, also reduced inhibition of brain acetylcholinesterase activity in rats dosed with methyl parathion (2.5 mg/kg intraperitoneally), while pretreatment with the herbicide linuron decreased acetylcholine brain levels below those found with methyl parathion treatment alone (Tvede et al. 1989). 

Auxins produce many changes in cells, including increased wall plasticity, enhanced respiratory rate and alterations in nucleic acid metabolism. Although the primary mode of action of auxins is not fully understood the development of the chemistry has progressed rapidly. Early discoveries identified and exploited the herbicide potential of super-optimal concentrations of auxin (Chapter 2, Herbicides) but their... 

Weed Resistance Based on Enhanced Herbicide Metabolism... 

In other weed biotypes, resistance to triazine herbicides is likely conferred by rapid metabolism of the herbicides to inactive compounds. A chlorotoluron-resistant biotype of blackgrass (slender foxtail) was cross-resistant to various other groups of herbicides, including triazines (Kemp et al., 1990). The mechanism of chlorotoluron resistance was Cyt P450-based enhanced oxidative metabolism through /V-demethylation and ring-methyl hydroxylation (Moss and Cussans, 1991). Consequently, it is likely that resistance to triazines in this blackgrass biotype is also due to enhanced herbicide detoxification. 

In summary, triazine resistance in weeds is most commonly due to a target site alteration that confers a very high level of resistance to. y-triazinc herbicides. Although a Ser264 to Gly mutation in the D1 protein is most common, additional alterations have been identified that confer resistance to triazines and other classes of PS II inhibitors. Enhanced herbicide metabolism plays a major role in conferring resistance in only a few weed biotypes. In these biotypes, the pattern of resistance may be broader, with some cross-resistance to av-trazinones, uracils, heterocyclic ureas and phenyl ureas. The level and pattern of resistance to various herbicides in these biotypes depend, presumably, on the activity and specificity of the enzyme(s) responsible for the enhanced herbicide metabolism. 

Adapted species may have developed, however, strategies which enable them to survive allelopathic attacks. One of those strategies certainly includes detoxification of absorbed allelochemicals by constitutive or inducible pathways. Metabolization and detoxification are known reactions in a number of crops upon application of diverse synthetic herbicides.38 Enhanced herbicide detoxification is an important factor in the development of nontarget-site cross-resistance and multiple resistance. It is reasonable to expect comparable strategies in plants that are relatively resistant to allelochemicals such as DIBOA, DIMBOA, and their derivatives. Especially in ecosystems where co-existing species have to be adapted to each other, detoxification of absorbed allelochemicals may play a crucial role under defined circumstances. 

The structure/activity studies seemed to support the idea that the antidote R-25788 (or its analogues) may act as a competitive inhibitor at site(s) of EPTC action in corn. These latter two theories of "antidote enhanced herbicide metabolism" versus "competitive inhibition" were hard to reconcile with each other. 

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